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Volume 51(1); January 2017
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Editorial
History of the Official Journal Published by the Korean Society of Pathologists: From the Korean Journal of Pathology to the Journal of Pathology and Translational Medicine
Se Hoon Kim, Chong Jai Kim, SoonWon Hong
J Pathol Transl Med. 2017;51(1):1-6.   Published online January 13, 2017
DOI: https://doi.org/10.4132/jptm.2017.01.07
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  • 1 Citations
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Letter to the Editor
Perivascular Epithelioid Cell Tumors (PEComas) of the Orbit
Panagiotis Paliogiannis, Giuseppe Palmieri, Francesco Tanda, Antonio Cossu
J Pathol Transl Med. 2017;51(1):7-8.   Published online January 5, 2017
DOI: https://doi.org/10.4132/jptm.2016.10.26
  • 6,084 View
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  • 4 Citations
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Original Articles
Increased Expression of Thymosin β4 Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer
Seung Yun Lee, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Chang Nam Kim, Joo Heon Kim, Dong Wook Kang
J Pathol Transl Med. 2017;51(1):9-16.   Published online October 16, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.23
  • 7,053 View
  • 149 Download
  • 5 Citations
AbstractAbstract PDF
Background
Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β4 expression in human colorectal cancers (CRCs).
Methods
We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series.
Results
High expression of thymosin β4 was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β4 showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β4 expression increased in parallel with HIF-1α expression in CRC.
Conclusions
A high expression level of thymosin β4 indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β4 is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.
Clinicopathologic Significance of Survivin Expression in Relation to CD133 Expression in Surgically Resected Stage II or III Colorectal Cancer
Wanlu Li, Mi-Ra Lee, EunHee Choi, Mee-Yon Cho
J Pathol Transl Med. 2017;51(1):17-23.   Published online December 15, 2016
DOI: https://doi.org/10.4132/jptm.2016.09.23
  • 7,554 View
  • 162 Download
  • 13 Citations
AbstractAbstract PDF
Background
Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples.
Methods
We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling.
Results
The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133+ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133+ versus 4.231 ± 3.812 in CD133– (p = .034).
Conclusions
As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC.
KRAS Mutation Test in Korean Patients with Colorectal Carcinomas: A Methodological Comparison between Sanger Sequencing and a Real-Time PCR-Based Assay
Sung Hak Lee, Arthur Minwoo Chung, Ahwon Lee, Woo Jin Oh, Yeong Jin Choi, Youn-Soo Lee, Eun Sun Jung
J Pathol Transl Med. 2017;51(1):24-31.   Published online December 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.10.03
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  • 3 Citations
AbstractAbstract PDFSupplementary Material
Background
Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti–epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment.
Methods
We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing.
Results
KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing–454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%.
Conclusions
The cobas test is an accurate and sensitive test for detecting KRAS-activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.
Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma
Hyun Min Koh, Bo Geun Jang, Chang Lim Hyun, Young Sill Kim, Jin Won Hyun, Weon Young Chang, Young Hee Maeng
J Pathol Transl Med. 2017;51(1):32-39.   Published online December 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.10.17
  • 7,033 View
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  • 17 Citations
AbstractAbstract PDF
Background
Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.
Methods
AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues.
Results
AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001).
Conclusions
AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.
PD-L1 Expression and Combined Status of PD-L1/PD-1–Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients
Jiheun Han, Yongkil Hong, Youn Soo Lee
J Pathol Transl Med. 2017;51(1):40-48.   Published online December 15, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.31
  • 12,114 View
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  • 27 Citations
AbstractAbstract PDF
Background
Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy.
Methods
PD-L1 expression and PD-1–positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated.
Results
PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053).
Conclusions
PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.
Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma
Yun Chai, Chang Gok Woo, Joo-Young Kim, Chong Jai Kim, Shin Kwang Khang, Jiyoon Kim, In Ah Park, Eun Na Kim, Kyu-Rae Kim
J Pathol Transl Med. 2017;51(1):49-55.   Published online October 14, 2016
DOI: https://doi.org/10.4132/jptm.2016.09.19
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  • 4 Citations
AbstractAbstract PDF
Background
Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT.
Methods
The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases.
Results
CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001).
Conclusions
Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.
Size of Non-lepidic Invasive Pattern Predicts Recurrence in Pulmonary Mucinous Adenocarcinoma: Morphologic Analysis of 188 Resected Cases with Reappraisal of Invasion Criteria
Soohyun Hwang, Joungho Han, Misun Choi, Myung-Ju Ahn, Yong Soo Choi
J Pathol Transl Med. 2017;51(1):56-68.   Published online October 16, 2016
DOI: https://doi.org/10.4132/jptm.2016.09.17
  • 7,851 View
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  • 3 Citations
AbstractAbstract PDF
Background
We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns.
Methods
Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3).
Results
The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121).
Conclusions
This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.
Evaluation of Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Experience in a Single Institution over a 10-Year Period
Misun Choi, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im, Seok Jin Nam, Soo Youn Cho, Eun Yoon Cho
J Pathol Transl Med. 2017;51(1):69-78.   Published online December 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.10.05
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  • 18 Citations
AbstractAbstract PDF
Background
Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. Methods: We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. Results: pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). Conclusions: Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.
Prognosis of Hepatocellular Carcinoma after Liver Transplantation: Comparative Analysis with Partial Hepatectomy
Kyuho Lee, Kyoung-Bun Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang
J Pathol Transl Med. 2017;51(1):79-86.   Published online December 25, 2016
DOI: https://doi.org/10.4132/jptm.2016.10.13
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  • 3 Citations
AbstractAbstract PDF
Background
Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). The aim of this study was to investigate the recurrence rate of HCC after LT and prognostic factors for recurrence by comparing LT with non-transplanted resection. Methods: The participants were 338 patients who underwent LT between 1996 and 2012 at Seoul National University Hospital (LT group) and 520 HCC patients who underwent partial hepatectomy between 1995 and 2006 (control group, non-LT group). Results: In the LT group, 68 of 338 patients (19.8%) showed relapse, and the recurrence rate was lower than that in the non-LT group (64.9%, 357/520, p < .001). Stratification analysis by American Joint Committee on Cancer (AJCC) stage showed that the stage I-II LT group had a lower recurrence rate than the non-LT group. Univariate comparative analysis demonstrated that multiplicity of tumor, tumor size, gross type, Edmondson- Steiner (ES) nuclear grade, extent of tumor, angioinvasion, AJCC stage, Milan criteria, University of California at San Francisco criteria on explant pathology (all p < .001), positive expression of cytokeratin 19 (p = .002), and preoperative α-fetoprotein (AFP) (p < .001) were predictors of tumor recurrence. In multivariate analysis, LT, preoperative AFP, multiplicity of tumor, extent of tumor, size of tumor, and ES nuclear grade were independent prognostic factors. Conclusions: LT might have a protective effect against the late recurrence of stage I-II HCC compared to non-LT, and the prognostic factors for recurrence were similar to previously well-known prognostic factors for HCC.
Case Studies
A Rare Case of Recurrent Metastatic Solid Pseudopapillary Neoplasm of the Pancreas
Hye Seung Lee, Han Kyeom Kim, Bong Kyung Shin, Jin Hyuk Choi, Yoo Jin Choi, Ha Yeon Kim
J Pathol Transl Med. 2017;51(1):87-91.   Published online August 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.16
  • 9,075 View
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  • 6 Citations
AbstractAbstract PDF
A 61-year-old woman visited our hospital for bilateral multiple lung nodules and a mass in her thorax. She had a long history of multiple metastatic recurrences of solid pseudopapillary neoplasm (SPN); 24 years previously, the patient had undergone pylorus-preserving pancreaticoduodenectomy for a 9.9 × 8.6 cm mass in the pancreatic head. The tumor was diagnosed as an SPN. Nine years later, metastatic nodules were found on computed tomography in the patient’s liver and peritoneum and were excised. She subsequently underwent an additional eight metastatectomy procedures in diverse organs. For the presented event, the lung nodules were removed. The prevalence of malignant SPN in the general population is 5%–15%. However, multiple metastatic recurrence of malignant SPN is rare; the lung is a particularly rare site of metastasis, found in only three cases in the literature. Here, we describe this exceptional case and provide a literature review.
A Rare Case of Angioleiomyoma Arising in the Subglottic Area to Upper Trachea of a Patient with Underlying Asthma
Yeoun Eun Sung, Chin Kook Rhee, Kyo Young Lee
J Pathol Transl Med. 2017;51(1):92-95.   Published online August 22, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.21
  • 6,820 View
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  • 3 Citations
AbstractAbstract PDF
Angioleiomyoma is a rare disease that is histologically characterized by smooth muscle cells arranged around vascular spaces. Although angioleiomyomas occur rarely in the head and neck region, they can cause various symptoms according the site involved. Here, we present a 44-yearold male patient with a 15-year history of asthma, who presented with recent onset of chest discomfort, globus sensation and throat pain. Medication was not effective in relieving his symptoms, and further evaluation revealed a polypoid ovoid mass, almost obstructing the airway at the border of the larynx and upper trachea on chest computed tomography. The mass was completely resected via a rigid bronchoscopy procedure. Histopathologic examination revealed that the excised mass was angioleiomyoma, which was immunohistochemically positive for smooth muscle actin and negative for desmin.
Brief Case Reports
Adult Intussusception Caused by Inverted Meckel’s Diverticulum Containing Mesenteric Heterotopic Pancreas and Smooth Muscle Bundles
Seungkoo Lee, Seong Whi Cho
J Pathol Transl Med. 2017;51(1):96-98.   Published online August 6, 2016
DOI: https://doi.org/10.4132/jptm.2016.06.15
  • 8,267 View
  • 125 Download
  • 2 Citations
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Human Herpes Virus 8/Epstein-Barr Virus–Copositive, Plasmablastic Microlymphoma Arising in Multicentric Castleman’s Disease of an Immunocompetent Patient
Yong-Moon Lee, Jin-Man Kim, Sam-Yong Kim
J Pathol Transl Med. 2017;51(1):99-102.   Published online December 24, 2016
DOI: https://doi.org/10.4132/jptm.2016.09.30
  • 6,618 View
  • 150 Download
  • 7 Citations
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JPTM : Journal of Pathology and Translational Medicine