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Case Study
EWSR1 rearranged primary renal myoepithelial carcinoma: a diagnostic conundrum
Nilay Nishith, Zachariah Chowdhury
J Pathol Transl Med. 2023;57(5):284-288.   Published online September 15, 2023
DOI: https://doi.org/10.4132/jptm.2023.08.08
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AbstractAbstract PDF
Primary renal myoepithelial carcinoma is an exceedingly rare neoplasm with an aggressive phenotype and Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement in a small fraction of cases. In addition to its rarity, the diagnosis can be challenging for the pathologist due to morphologic heterogeneity, particularly on the biopsy specimen. At times, immunohistochemistry may be indecisive; therefore, molecular studies should be undertaken for clinching the diagnosis. We aim to illustrate a case of primary myoepithelial carcinoma of the kidney with EWSR1-rearrangement in a 67-year-old male patient who presented with right supraclavicular mass, which was clinically diagnosed as carcinoma of an unknown primary. An elaborate immunohistochemical work-up aided by fluorescent in-situ hybridization allowed us to reach a conclusive diagnosis. This unusual case report advocates that one should be aware of the histological mimickers and begin with broad differential diagnoses alongside sporadic ones and then narrow them down with appropriate ancillary studies.
Original Article
Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study
Seokhyeon Lee, Bohyun Kim, Minsun Jung, Kyung Chul Moon
J Pathol Transl Med. 2023;57(4):232-237.   Published online July 11, 2023
DOI: https://doi.org/10.4132/jptm.2023.06.17
  • 1,293 View
  • 117 Download
AbstractAbstract PDF
Background
Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size.
Methods
We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression.
Results
High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC.
Conclusions
Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.
Case Study
Unusual biclonal IgA plasma cell myeloma with aberrant expression of high-risk immunophenotypes: first report of a new diagnostic and clinical challenge
Carlos A. Monroig-Rivera, Clara N. Finch Cruz
J Pathol Transl Med. 2023;57(2):132-137.   Published online March 14, 2023
DOI: https://doi.org/10.4132/jptm.2023.02.07
  • 1,010 View
  • 67 Download
AbstractAbstract PDF
IgA plasma cell myeloma (PCM) has been linked to molecular abnormalities that confer a higher risk for adverse patient outcomes. However, since IgA PCM only accounts for approximately 20% of all PCM, there are very few reports on high-risk IgA PCM. Moreover, no such reports are found on the more infrequent biclonal IgA PCM. Hence, we present a 65-year-old Puerto Rican female with acute abdominal pain, concomitant hypercalcemia, and acute renal failure. Protein electrophoresis with immunofixation found high IgA levels and detected a biclonal IgA gammopathy with kappa specificity. Histomorphologically, bone marrow showed numerous abnormal plasma cells (32%) replacing over 50% of the marrow stroma. Immunophenotyping analysis detected CD45-negative plasma cells aberrantly expressing CD33, CD43, OCT-2, and c-MYC. Chromosomal analysis revealed multiple abnormalities including the gain of chromosome 1q. Thus, we report on an unusual biclonal IgA PCM and the importance of timely diagnosing aggressive plasma cell neoplasms.
Original Article
Prognostic and clinicopathological significance of Fusobacterium nucleatum in colorectal cancer: a systemic review and meta-analysis
Younghoon Kim, Nam Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2022;56(3):144-151.   Published online May 15, 2022
DOI: https://doi.org/10.4132/jptm.2022.03.13
  • 3,256 View
  • 112 Download
  • 4 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary Material
Background
Fusobacterium nucleatum has been identified to promote tumor progression in colorectal cancer (CRC). However, association between F. nucleatum and prognostic or clinicopathological features has been diverse among studies, which could be affected by type of biospecimen (formalin-fixed paraffin-embedded or fresh frozen [FF]).
Methods
Articles were systemically reviewed for studies that included the correlation between F. nucleatum and prognosis or clinicopathological features in CRC.
Results
Ten articles, eight studies with survival-related features involving 3,199 patients and nine studies with clinical features involving 2,655 patients, were eligible for the meta-analysis. Overall survival, disease-free survival, and cancer-specific survival were all associated with worse prognosis in F. nucleatum–high patients (p<.05). In subgroup analysis, only studies with FF tissues retained prognostic significance with F. nucleatum. In meta-analysis of clinicopathological variables, F. nucleatum level was associated with location within colon, pT category, MLH1 hypermethylation, microsatellite instability status, and BRAF mutation regardless of type of biospecimen. However, lymph node metastasis and KRAS mutation was only associated with F. nucleatum level in FF-based studies.
Conclusions
In conclusion, type of biospecimen could affect the role of F. nucleatum as a biomarker associated with clinicopathological features and prognosis.

Citations

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  • Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer
    Jihoon E. Joo, Yen Lin Chu, Peter Georgeson, Romy Walker, Khalid Mahmood, Mark Clendenning, Aaron L. Meyers, Julia Como, Sharelle Joseland, Susan G. Preston, Natalie Diepenhorst, Julie Toner, Danielle J. Ingle, Norelle L. Sherry, Andrew Metz, Brigid M. Ly
    British Journal of Cancer.2024; 130(5): 728.     CrossRef
  • Fusobacterium nucleatum Load Correlates with KRAS Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma
    Koki Takeda, Minoru Koi, Yoshiki Okita, Sija Sajibu, Temitope O. Keku, John M. Carethers
    Cancer Research Communications.2023; 3(9): 1940.     CrossRef
  • Tumour Colonisation of Parvimonas micra Is Associated with Decreased Survival in Colorectal Cancer Patients
    Thyra Löwenmark, Anna Löfgren-Burström, Carl Zingmark, Ingrid Ljuslinder, Michael Dahlberg, Sofia Edin, Richard Palmqvist
    Cancers.2022; 14(23): 5937.     CrossRef
Review
Follicular lymphoma: updates for pathologists
Mahsa Khanlari, Jennifer R. Chapman
J Pathol Transl Med. 2022;56(1):1-15.   Published online December 27, 2021
DOI: https://doi.org/10.4132/jptm.2021.09.29
  • 7,228 View
  • 583 Download
  • 7 Web of Science
  • 6 Crossref
AbstractAbstract PDF
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.

Citations

Citations to this article as recorded by  
  • The follicular lymphoma tumor microenvironment at single-cell and spatial resolution
    Andrea J. Radtke, Mark Roschewski
    Blood.2024; 143(12): 1069.     CrossRef
  • Transformation of low-grade follicular lymphoma to a high-grade follicular lymphoma with the histopathological diagnosis from oral biopsy: a case report
    Gabriela Silveira de Araujo, Leandro Dorigan de Macedo, Alfredo Ribeiro-Silva, Hilton Marcos Alves Ricz, Lara Maria Alencar Ramos Innocentini
    Hematology, Transfusion and Cell Therapy.2023;[Epub]     CrossRef
  • Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis
    Hao Wu, Hui-Cong Sun, Gui-Fang Ouyang
    World Journal of Clinical Cases.2023; 11(14): 3176.     CrossRef
  • A rare case of follicular lymphoma of the bladder
    Matthew DeSanto, Robert Strait, Jared Zopp, Kevin Brown, Samuel Deem
    Urology Case Reports.2023; 51: 102542.     CrossRef
  • Analysis of immunophenotypic features in hyaline vascular type Castleman disease
    Yu Chang, Yu Ma, Chen Chang, Wensheng Li
    Diagnostic Pathology.2023;[Epub]     CrossRef
  • A review of the totality of evidence in the development of ABP 798, a rituximab biosimilar
    Patrick Cobb, Dietger Niederwieser, Stanley Cohen, Caroline Hamm, Gerd Burmester, Neungseon Seo, Sonya G Lehto, Vladimir Hanes
    Immunotherapy.2022; 14(9): 727.     CrossRef
Original Articles
Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment
Yoon Jung Hwang, Youngeun Lee, Hyunjin Park, Yangkyu Lee, Kyoungbun Lee, Haeryoung Kim
J Pathol Transl Med. 2021;55(5):338-348.   Published online September 2, 2021
DOI: https://doi.org/10.4132/jptm.2021.07.26
  • 2,634 View
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  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary Material
Background
Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS).
Methods
A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival.
Results
As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm.
Conclusions
Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

Citations

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  • Construction and validation of a novel signature based on epithelial-mesenchymal transition–related genes to predict prognosis and immunotherapy response in hepatocellular carcinoma by comprehensive analysis of the tumor microenvironment
    Biao Gao, Yafei Wang, Shichun Lu
    Functional & Integrative Genomics.2023;[Epub]     CrossRef
  • Cellular senescence affects energy metabolism, immune infiltration and immunotherapeutic response in hepatocellular carcinoma
    Biao Gao, Yafei Wang, Shichun Lu
    Scientific Reports.2023;[Epub]     CrossRef
Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations
Dalia Elsers, Doaa F. Temerik, Alia M. Attia, A. Hadia, Marwa T. Hussien
J Pathol Transl Med. 2021;55(3):212-224.   Published online May 11, 2021
DOI: https://doi.org/10.4132/jptm.2021.03.15
  • 3,267 View
  • 115 Download
  • 3 Web of Science
  • 4 Crossref
AbstractAbstract PDF
Background
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM).
Methods
The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry.
Results
Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS.
Conclusions
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

Citations

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  • Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis
    Rongxuan Hua, Qiuxuan Li, Han Gao, Boya Wang, Chengwei He, Ying Wang, Sitian Zhang, Lei Gao, Hongwei Shang, Wen Wang, Jingdong Xu
    Journal of Research in Medical Sciences.2023; 28(1): 47.     CrossRef
  • Immunohistochemical surrogates for molecular alterations for the classification and grading of gliomas
    Viharkumar Patel, Sanda Alexandrescu
    Seminars in Diagnostic Pathology.2022; 39(1): 78.     CrossRef
  • Meme Kanseri Hastalarında hTERT Gen Ekspresyonunun Klinikopatolojik Önemi
    Ebubekir DİRİCAN, Burak KANKAYA, Zeynep TATAR
    Sağlık Bilimlerinde Değer.2022; 12(1): 22.     CrossRef
  • Prognostic and predictive markers in glioblastoma and ALK overexpression
    Jang-Hee Kim
    Journal of Pathology and Translational Medicine.2021; 55(3): 236.     CrossRef
MicroRNA-552 expression in colorectal cancer and its clinicopathological significance
Joon Im, Soo Kyung Nam, Hye Seung Lee
J Pathol Transl Med. 2021;55(2):125-131.   Published online February 19, 2021
DOI: https://doi.org/10.4132/jptm.2021.01.17
  • 2,992 View
  • 111 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary Material
Background
MicroRNA-552 (miR-552) has been reported to correlate with the development and progression of various cancers, including colorectal cancer (CRC). This study aimed to investigate miR-552 expression in cancer tissue samples compared to normal mucosal tissue and its role as a diagnostic or prognostic marker in CRC patients.
Methods
Normal mucosal tissues and primary cancer tissues from 80 surgically resected CRC specimens were used. Quantitative real-time polymerase chain reaction was performed for miR-552 and U6 small nuclear RNA to analyze miR-552 expression and its clinicopathological significance. Immunohistochemistry for p53 and phosphatase and tension homolog (PTEN) was performed to evaluate their association with miR-552 expression.
Results
miR-552 expression was significantly higher in primary cancer tissues compared to normal mucosal tissues (p<.001). The expression level of miR552 was inversely correlated with that of PTEN (p=.068) and p53 (p=.004). Survival analysis showed that high miR-552 expression was associated with worse prognosis but this was not statistically significant (p=.255). However, patients with CRC having high miR-552 expression and loss of PTEN expression had significantly worse prognosis than others (p=.029).
Conclusions
Our results suggest that high miR-552 expression might be a potential diagnostic biomarker for CRC, and its combined analysis with PTEN expression can possibly be used as a prognostic marker.

Citations

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  • Integration of TE Induces Cancer Specific Alternative Splicing Events
    Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Woo Hyeon Bae, Du Hyeong Lee, Heui-Soo Kim
    International Journal of Molecular Sciences.2022; 23(18): 10918.     CrossRef
The prognostic significance of p16 expression pattern in diffuse gliomas
Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park
J Pathol Transl Med. 2021;55(2):102-111.   Published online December 23, 2020
DOI: https://doi.org/10.4132/jptm.2020.10.22
  • 5,748 View
  • 276 Download
  • 16 Web of Science
  • 12 Crossref
AbstractAbstract PDF
Background
CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.
Methods
p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.
Results
A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).
Conclusions
This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.

Citations

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  • Revealing the role of necroptosis microenvironment: FCGBP + tumor-associated macrophages drive primary liver cancer differentiation towards cHCC-CCA or iCCA
    Chun Wang, Cuimin Chen, Wenting Hu, Lili Tao, Jiakang Chen
    Apoptosis.2024; 29(3-4): 460.     CrossRef
  • FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma
    Sofian Al Shboul, Shelagh Boyle, Ashita Singh, Tareq Saleh, Moath Alrjoub, Ola Abu Al Karsaneh, Amel Mryyian, Rand Dawoud, Sinem Gul, Shaden Abu Baker, Kathryn Ball, Ted Hupp, Paul M. Brennan
    Brain Tumor Pathology.2024; 41(1): 4.     CrossRef
  • p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?
    Roberto Gallus, Davide Rizzo, Giorgia Rossi, Luca Mureddu, Jacopo Galli, Alberto Artuso, Francesco Bussu
    Pathogens.2024; 13(2): 100.     CrossRef
  • CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization
    Manali Ranade, Sridhar Epari, Omshree Shetty, Sandeep Dhanavade, Sheetal Chavan, Ayushi Sahay, Arpita Sahu, Prakash Shetty, Aliasgar Moiyadi, Vikash Singh, Archya Dasgupta, Abhishek Chatterjee, Sadhana Kannan, Tejpal Gupta
    Journal of Neuro-Oncology.2024;[Epub]     CrossRef
  • Molecular prognostication in grade 3 meningiomas and p16/MTAP immunohistochemistry for predicting CDKN2A/B status
    Kira Tosefsky, Karina Chornenka Martin, Alexander D Rebchuk, Justin Z Wang, Farshad Nassiri, Amy Lum, Gelareh Zadeh, Serge Makarenko, Stephen Yip
    Neuro-Oncology Advances.2024;[Epub]     CrossRef
  • p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances
    Lucas Geyer, Thibaut Wolf, Marie-Pierre Chenard, Helene Cebula, Roland Schott, Georges Noel, Eric Guerin, Erwan Pencreach, Damien Reita, Natacha Entz-Werlé, Benoît Lhermitte
    Cancers.2023; 15(5): 1512.     CrossRef
  • P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas
    Meenakshi Vij, Benjamin B. Cho, Raquel T. Yokoda, Omid Rashidipour, Melissa Umphlett, Timothy E. Richardson, Nadejda M. Tsankova
    Acta Neuropathologica Communications.2023;[Epub]     CrossRef
  • CDKN2A mutations have equivalent prognostic significance to homozygous deletion in IDH-mutant astrocytoma
    Raquel T Yokoda, William S Cobb, Raymund L Yong, John F Crary, Mariano S Viapiano, Jamie M Walker, Melissa Umphlett, Nadejda M Tsankova, Timothy E Richardson
    Journal of Neuropathology & Experimental Neurology.2023; 82(10): 845.     CrossRef
  • Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning
    Gi Jeong Kim, Tonghyun Lee, Sangjeong Ahn, Youngjung Uh, Se Hoon Kim
    npj Precision Oncology.2023;[Epub]     CrossRef
  • Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors
    Hyunhee Kim, Ka Young Lim, Jin Woo Park, Jeongwan Kang, Jae Kyung Won, Kwanghoon Lee, Yumi Shim, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi, Tae Min Kim, Hongseok Yun, Sung-Hye Park
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    Maher Kurdi, Rana H Moshref, Yousef Katib, Eyad Faizo, Ahmed A Najjar, Basem Bahakeem, Ahmed K Bamaga
    World Journal of Clinical Oncology.2022; 13(7): 567.     CrossRef
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    Hasan Safwan-Zaiter, Nicole Wagner, Kay-Dietrich Wagner
    Life.2022; 12(9): 1332.     CrossRef
A comparative prognostic performance of definitions of Crohn-like lymphoid reaction in colorectal carcinoma
Younghoon Kim, Jeong Mo Bae, Jung Ho Kim, Nam-Yun Cho, Gyeong Hoon Kang
J Pathol Transl Med. 2021;55(1):53-59.   Published online November 27, 2020
DOI: https://doi.org/10.4132/jptm.2020.10.06
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AbstractAbstract PDFSupplementary Material
Background
The prognostic potential of Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) has been investigated through the assessment of different criteria.
Methods
The prognostic impact of CLR was investigated in 636 CRC patients to compare methods from previously published articles. These methods included CLR measured by number of lymphoid aggregates (LAs) (CLR count), LA size greater than or equal to 1 mm (CLR size), CLR density with a cutoff value of 0.38, and subjective criteria as defined by intense CLR.
Results
In univariate survival analysis, CLR-positive CRC as defined by the four aforementioned methods was associated with better overall survival (OS) (hazard ratio [HR], 0.463; 95% confidence interval [CI], 0.305 to 0.702; p <.001; HR, 0.656; 95% CI, 0.411 to 1.046; p=.077; HR, 0.363; 95% CI, 0.197 to 0.669; p=.001; and HR, 0.433; 95% CI, 0.271 to 0.690; p<.001, respectively) and disease-free survival (DFS) (HR, 0.411; 95% CI, 0.304 to 0.639; p<.001; HR, 0.528; 95% CI, 0.340 to 0.821; p=.004; HR, 0.382; 95% CI, 0.226 to 0.645, p=.004; and HR, 0.501; 95% CI, 0.339 to 0.741; p<.001, respectively) than CLR-negative CRC, regardless of criteria with the exception of OS for CLR density. In multivariate analysis, two objective criteria (CLR count and CLR density) and one subjective criterion (intense CLR) for defining CLR were considered independent prognostic factors of OS and DFS in CRC patients.
Conclusions
CLR has similar traits regardless of criteria, but CLR-positivity should be defined by objective criteria for better reproducibility and prognostic value.
Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer
Ji Hye Kim, Kyungbin Kim, Misung Kim, Young Min Kim, Jae Hee Suh, Hee Jeong Cha, Hye Jeong Choi
J Pathol Transl Med. 2020;54(2):154-164.   Published online February 10, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.13
  • 6,679 View
  • 153 Download
  • 14 Web of Science
  • 13 Crossref
AbstractAbstract PDF
Background
Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC).
Methods
We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed.
Results
PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05).
Conclusions
The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.

Citations

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  • Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis
    Giorgio Frega, Fernando P. Cossio, Jesus M. Banales, Vincenzo Cardinale, Rocio I. R. Macias, Chiara Braconi, Angela Lamarca
    Cells.2023; 12(16): 2098.     CrossRef
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    Whayoung Lee, Vishal S. Chandan
    Human Pathology.2023; 132: 149.     CrossRef
  • Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions
    Neetu Rawal, Supriya Awasthi, Nihar Ranjan Dash, Sunil Kumar, Prasenjit Das, Amar Ranjan, Anita Chopra, Maroof Ahmad Khan, Sundeep Saluja, Showket Hussain, Pranay Tanwar
    Current Oncology.2023; 30(2): 1571.     CrossRef
  • Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer
    Ishita Ghosh, Ruma Dey Ghosh, Soma Mukhopadhyay
    World Journal of Gastrointestinal Oncology.2023; 15(12): 2053.     CrossRef
  • CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer
    Lu Cao, Kim R. Bridle, Ritu Shrestha, Prashanth Prithviraj, Darrell H. G. Crawford, Aparna Jayachandran
    International Journal of Molecular Sciences.2022; 23(3): 1565.     CrossRef
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    Frontiers in Immunology.2022;[Epub]     CrossRef
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    Frontiers in Oncology.2022;[Epub]     CrossRef
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    You-Na Sung, Sung Joo Kim, Sun-Young Jun, Changhoon Yoo, Kyu-Pyo Kim, Jae Hoon Lee, Dae Wook Hwang, Shin Hwang, Sang Soo Lee, Seung-Mo Hong
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Pallavi A. Patil, Kara Lombardo, Weibiao Cao
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    Matteo Canale, Manlio Monti, Ilario Giovanni Rapposelli, Paola Ulivi, Francesco Giulio Sullo, Giulia Bartolini, Elisa Tiberi, Giovanni Luca Frassineti
    Cancers.2021; 13(22): 5671.     CrossRef
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    Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
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Expression of female sex hormone receptors and its relation to clinicopathological characteristics and prognosis of lung adenocarcinoma
Jin Hwan Lee, Han Kyeom Kim, Bong Kyung Shin
J Pathol Transl Med. 2020;54(1):103-111.   Published online November 13, 2019
DOI: https://doi.org/10.4132/jptm.2019.10.12
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AbstractAbstract PDF
Background
Adenocarcinoma (ADC) of the lung exhibits different clinicopathological characteristics in men and women. Recent studies have suggested that these differences originate from the expression of female sex hormone receptors in tumor cells. The aim of the present study was to evaluate the immunohistochemical expression of female sex hormone receptors in lung ADC and determine the expression patterns in patients with different clinicopathological characteristics.
Methods
A total of 84 patients with lung ADC who underwent surgical resection and/or core biopsy were recruited for the present study. Immunohistochemical staining was performed for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR), epidermal growth factor receptor (EGFR), EGFR E746- A750 del, and EGFR L858R using tissue microarray.
Results
A total of 39 (46.4%) ERα-positive, 71 (84.5%) ERβ-positive, and 46 (54.8%) PR-positive lung ADCs were identified. In addition, there were 81 (96.4%) EGFR-positive, 14 (16.7%) EGFR E746-A750 del–positive, and 34 (40.5%) EGFR L858R–positive cases. The expression of female sex hormone receptors was not significantly different in clinicopathologically different subsets of lung ADC.
Conclusions
Expression of female sex hormone receptors is not associated with the prognosis and clinicopathological characteristics of patients with lung ADC.

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  • Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review
    Carmine Valenza, Francesca Maria Porta, Alessandra Rappa, Elena Guerini-Rocco, Giuseppe Viale, Massimo Barberis, Filippo de Marinis, Giuseppe Curigliano, Chiara Catania
    Current Oncology.2021; 28(5): 3384.     CrossRef
  • Development of a 15-Gene Signature Model as a Prognostic Tool in Sex Hormone-Dependent Cancers
    Zhi Xia, Jian Xiao, Aibin Liu, Qiong Chen, Arumugam R. Jayakumar
    BioMed Research International.2021; 2021: 1.     CrossRef
  • Gender-specific aspects of epidemiology, molecular genetics and outcome: lung cancer
    Nuria Mederos, Alex Friedlaender, Solange Peters, Alfredo Addeo
    ESMO Open.2020; 5(Suppl 4): e000796.     CrossRef
Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma
Seung-Yeon Yoo, Ji-Ae Lee, Yunjoo Shin, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang
J Pathol Transl Med. 2019;53(5):289-297.   Published online June 24, 2019
DOI: https://doi.org/10.4132/jptm.2019.06.07
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  • 144 Download
  • 7 Web of Science
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AbstractAbstract PDFSupplementary Material
Background
SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC.
Methods
We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs.
Results
A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancerspecific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022).
Conclusions
We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.

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  • Unraveling Resistance to Immunotherapy in MSI-High Colorectal Cancer
    Ronald Heregger, Florian Huemer, Markus Steiner, Alejandra Gonzalez-Martinez, Richard Greil, Lukas Weiss
    Cancers.2023; 15(20): 5090.     CrossRef
  • Association of β-Catenin, APC, SMAD3/4, Tp53, and Cyclin D1 Genes in Colorectal Cancer: A Systematic Review and Meta-Analysis
    Hongfeng Yan, Fuquan Jiang, Jianwu Yang, Ying-Kun Xu
    Genetics Research.2022; 2022: 1.     CrossRef
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    Jiwon Koh, Soo Kyung Nam, Yoonjin Kwak, Gilhyang Kim, Ka‐Kyung Kim, Byung‐Chul Lee, Sang‐Hoon Ahn, Do Joong Park, Hyung‐Ho Kim, Kyoung Un Park, Woo Ho Kim, Hye Seung Lee
    The Journal of Pathology.2021; 253(1): 94.     CrossRef
  • Alterations of PTEN and SMAD4 methylation in diagnosis of breast cancer: implications of methyl II PCR assay
    Menha Swellam, Entsar A. Saad, Shimaa Sabry, Adel Denewer, Camelia Abdel Malak, Amr Abouzid
    Journal of Genetic Engineering and Biotechnology.2021; 19(1): 54.     CrossRef
  • Molecular Characterization and Functional Analysis of Two Steroidogenic Genes TSPO and SMAD4 in Yellow Catfish
    Fang Chen, Chong-Chao Zhong, Chang-Chun Song, Shu-Wei Chen, Yang He, Xiao-Ying Tan
    International Journal of Molecular Sciences.2021; 22(9): 4505.     CrossRef
  • SMAD7 and SMAD4 expression in colorectal cancer progression and therapy response
    Jovana Rosic, Sandra Dragicevic, Marko Miladinov, Jovana Despotovic, Aleksandar Bogdanovic, Zoran Krivokapic, Aleksandra Nikolic
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Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer
So Young Kim, Kyung Un Choi, Chungsu Hwang, Hyung Jung Lee, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Jae Ho Kim, Ki Hyung Kim, Dong Soo Suh, Byung Su Kwon
J Pathol Transl Med. 2019;53(4):244-252.   Published online May 2, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.16
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AbstractAbstract PDF
Background
Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis.
Methods
Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy.
Results
CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001).
Conclusions
Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.

Citations

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  • CD109 Promotes Drug Resistance in A2780 Ovarian Cancer Cells by Regulating the STAT3-NOTCH1 Signaling Axis
    Jun Se Kim, Min Joo Shin, Seo Yul Lee, Dae Kyoung Kim, Kyung-Un Choi, Dong-Soo Suh, Dayea Kim, Jae Ho Kim
    International Journal of Molecular Sciences.2023; 24(12): 10306.     CrossRef
  • CD109 facilitates progression and 5-fluorouracil resistance of nasopharyngeal carcinoma
    Zhenwei Zhu, Fang Zhou, Cheng Mao
    Materials Express.2022; 12(9): 1189.     CrossRef
  • Usefulness of CD109 expression as a prognostic biomarker in patients with cancer
    Hyun Min Koh, Hyun Ju Lee, Dong Chul Kim
    Medicine.2021; 100(11): e25006.     CrossRef
  • Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma
    Sumitaka Hagiwara, Eiichi Sasaki, Yasuhisa Hasegawa, Hidenori Suzuki, Daisuke Nishikawa, Shintaro Beppu, Hoshino Terada, Michi Sawabe, Masahide Takahashi, Nobuhiro Hanai
    Cancer Medicine.2021; 10(4): 1335.     CrossRef
Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis
Jung-Soo Pyo, Nae Yu Kim, Won Jin Cho
J Pathol Transl Med. 2019;53(3):173-179.   Published online March 5, 2019
DOI: https://doi.org/10.4132/jptm.2019.02.03
  • 5,900 View
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  • 4 Crossref
AbstractAbstract PDF
Background
Although the correlation between low claudin-1 expression and worse prognosis has been reported, details on the prognostic implications of claudin-1 expression in various malignant tumors remain unclear. The present study aimed to elucidate the prognostic roles of claudin- 1 immunohistochemistry (IHC) in various malignant tumors through a meta-analysis.
Methods
The study included 2,792 patients from 22 eligible studies for assessment of the correlation between claudin-1 expression and survival rate in various malignant tumors. A subgroup analysis based on the specific tumor and evaluation criteria of claudin-1 IHC was conducted.
Results
Low claudin-1 expression was significantly correlated with worse overall survival (OS) (hazard ratio [HR], 1.851; 95% confidence interval [CI], 1.506 to 2.274) and disease-free survival (DFS) (HR, 2.028; 95% CI, 1.313 to 3.134) compared to high claudin-1 expression. Breast, colorectal, esophageal, gallbladder, head and neck, and lung cancers, but not cervical, liver or stomach cancers, were significantly correlated with worse OS. Breast, colorectal, esophageal, and thyroid cancers with low claudin-1 expression were associated with poorer DFS. In the lower cut-off subgroup (< 25.0%) with respect to claudin-1 IHC, low claudin-1 expression was significantly correlated with worse OS and DFS.
Conclusions
Taken together, low claudin-1 IHC expression is significantly correlated with worse survival in various malignant tumors. More detailed criteria for claudin-1 IHC expression in various malignant tumors are needed for application in daily practice.

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    Ekarat Phattarataratip, Kraisorn Sappayatosok
    Head and Neck Pathology.2020; 14(2): 480.     CrossRef
  • Claudin-1 upregulation is associated with favorable tumor features and a reduced risk for biochemical recurrence in ERG-positive prostate cancer
    Simon Kind, Franziska Büscheck, Doris Höflmayer, Claudia Hube-Magg, Martina Kluth, Maria Christina Tsourlakis, Stefan Steurer, Till S. Clauditz, Andreas M. Luebke, Eike Burandt, Waldemar Wilczak, Andrea Hinsch, David Dum, Sören Weidemann, Christoph Fraune
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  • Characterisation of endogenous Claudin‐1 expression, motility and susceptibility to hepatitis C virus in CRISPR knock‐in cells
    Camille M.H. Clément, Maika S. Deffieu, Cristina M. Dorobantu, Thomas F. Baumert, Nilda Vanesa Ayala‐Nunez, Yves Mély, Philippe Ronde, Raphael Gaudin
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  • Comment on “Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis”
    Bolin Wang, Yan Huang
    Journal of Pathology and Translational Medicine.2019; 53(6): 411.     CrossRef

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