Journal of Pathology and Translational Medicine

Case Study

Thyroid pathology, a clue to PTEN hamartoma tumor syndrome: Yurimi Lee, Young Lyun Oh; J Pathol Transl Med. 2023;57(3):178-183. Published online March 30, 2023; DOI: https://doi.org/10.4132/jptm.2023.03.04

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Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations in the PTEN tumor suppressor gene. As a type of PHTS, Cowden syndrome is associated with abnormalities of the thyroid, breast, uterus, and gastrointestinal tract. A 52-year-old-woman visited the outpatient clinic of our endocrinology clinic with multiple thyroid nodules and Hashimoto's thyroiditis. Computed tomography imaging revealed a multinodular mass measuring up to 3.5 cm in the left thyroid lobe, causing laryngotracheal airway displacement. The total thyroidectomy specimen revealed multiple follicular adenomas and adenomatous nodules with lymphocytic thyroiditis and lipomatous metaplasia in the background. The patient was suspected of PTHS based on her thyroid pathology, family history, and numerous hamartomatous lesions of the breast, uterus, and skin. Her diagnosis was confirmed through molecular testing. This case demonstrates that pathologists must be well acquainted with thyroid pathology in PHTS.

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
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Case report: Rare oral manifestations in Cowden syndrome with PTEN mutation
Wei Yuan, Yanbin Liu, Haibin Sun, Ming Su, Lizheng Qin, Xin Huang
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Original Articles

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

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Abstract PDF Supplementary 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.

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Blood miRNAs miR-549a, miR-552, and miR-592 serve as potential disease-specific panels to diagnose colorectal cancer
Soroush Akbar, Samaneh Mashreghi, Mohammad Reza Kalani, Akram Valanik, Farzaneh Ahmadi, Mahdi Aalikhani, Zahra Bazi
Heliyon.2024; 10(7): e28492. CrossRef
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 Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma: Yumin Chung, Young Chan Wi, Yeseul Kim, Seong Sik Bang, Jung-Ho Yang, Kiseok Jang, Kyueng-Whan Min, Seung Sam Paik; J Pathol Transl Med. 2018;52(1):37-44. Published online October 23, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.20

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Abstract PDF Supplementary Material

Background
Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma.
Methods
Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed.
Results
Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05).
Conclusions
Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

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The Potential Role of Genomic Signature in Stage II Relapsed Colorectal Cancer (CRC) Patients: A Mono-Institutional Study
Michela Roberto, Giulia Arrivi, Emanuela Pilozzi, Andrea Montori, Genoveffa Balducci, Paolo Mercantini, Andrea Laghi, Debora Ierinò, Martina Panebianco, Daniele Marinelli, Silverio Tomao, Paolo Marchetti, Federica Mazzuca
Cancer Management and Research.2022; Volume 14: 1353. 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
E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4
Chen Lu, Guangyao Ning, Panpan Si, Chunsheng Zhang, Wenjian Liu, Wei Ge, Kai Cui, Renquan Zhang, Shenglin Ge
Biochemistry and Cell Biology.2021; 99(5): 675. CrossRef
Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells
Sara Sommariva, Giacomo Caviglia, Silvia Ravera, Francesco Frassoni, Federico Benvenuto, Lorenzo Tortolina, Nicoletta Castagnino, Silvio Parodi, Michele Piana
Scientific Reports.2021;[Epub] CrossRef
Clinicopathological characterization of SMAD4-mutated intestinal adenocarcinomas: A case-control study
Xiaoyan Liao, Yansheng Hao, Xiaofei Zhang, Stephen Ward, Jane Houldsworth, Alexandros D. Polydorides, Noam Harpaz, Aldo Scarpa
PLOS ONE.2019; 14(2): e0212142. 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
Journal of Pathology and Translational Medicine.2019; 53(5): 289. CrossRef
Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
Ion Cristóbal, Blanca Torrejón, Andrea Santos, Melani Luque, Marta Sanz-Alvarez, Federico Rojo, Jesús García-Foncillas
European Journal of Surgical Oncology.2018; 44(8): 1283. CrossRef
Reply to: Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
Jordan M. Cloyd, Takashi Mizuno, Jean-Nicolas Vauthey
European Journal of Surgical Oncology.2018; 44(8): 1285. CrossRef

Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors: Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh; Korean J Pathol. 2014;48(1):17-23. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.17

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Abstract PDF

Background

Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.

Methods

Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).

Results

Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).

Conclusions

This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

Citations

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Role of microRNAs in regulating cell proliferation, metastasis and chemoresistance and their applications as cancer biomarkers in small cell lung cancer
Monu Pandey, Abhirup Mukhopadhyay, Surender K. Sharawat, Sachin Kumar
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2021; 1876(1): 188552. CrossRef
Neuroendocrine Tumors Are Enriched in Cowden Syndrome
Alison Greidinger, Susan Miller-Samuel, Veda N. Giri, Michele Sue-Ann Woo, Saranya Akumalla, Charnita Zeigler-Johnson, Scott W. Keith, Daniel P. Silver
JCO Precision Oncology.2020; (4): 551. CrossRef
Prognostic and predictive role of the PI3K–AKT–mTOR pathway in neuroendocrine neoplasms
P. Gajate, T. Alonso-Gordoa, O. Martínez-Sáez, J. Molina-Cerrillo, E. Grande
Clinical and Translational Oncology.2018; 20(5): 561. CrossRef
Genetic and epigenetic drivers of neuroendocrine tumours (NET)
Annunziata Di Domenico, Tabea Wiedmer, Ilaria Marinoni, Aurel Perren
Endocrine-Related Cancer.2017; 24(9): R315. CrossRef
Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung
Pietro Di Fazio, Moritz Maass, Silvia Roth, Christian Meyer, Joana Grups, Peter Rexin, Detlef K Bartsch, Andreas Kirschbaum
Tumor Biology.2017; 39(10): 101042831772841. CrossRef
The regulatory role of aberrant Phosphatase and Tensin Homologue and Liver Kinase B1 on AKT/mTOR/c-Myc axis in pancreatic neuroendocrine tumors
Tsung-Ming Chang, Yan-Shen Shan, Pei-Yi Chu, Shih Sheng Jiang, Wen-Chun Hung, Yu-Lin Chen, Hsiu-Chi Tu, Hui-You Lin, Hui-Jen Tsai, Li-Tzong Chen
Oncotarget.2017; 8(58): 98068. CrossRef
Pulmonary atypical carcinoid in a patient with Cowden syndrome
Hiroaki Tsunezuka, Kaori Abe, Junichi Shimada, Masayoshi Inoue
Interactive CardioVascular and Thoracic Surgery.2016; 22(6): 860. CrossRef
Differential miRNA-Expression as an Adjunctive Diagnostic Tool in Neuroendocrine Tumors of the Lung
Melanie Demes, Christoph Aszyk, Holger Bartsch, Joachim Schirren, Annette Fisseler-Eckhoff
Cancers.2016; 8(4): 38. CrossRef
microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway
Yu-Bin Meng, Xue Li, Zhao-Yang Li, Jin Zhao, Xu-Bo Yuan, Yu Ren, Zhen-Duo Cui, Yun-De Liu, Xian-Jin Yang
Journal of Orthopaedic Research.2015; 33(7): 957. CrossRef
Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21
Song Yan, Gang Liu, Changyan Pei, Wenqing Chen, Pei Li, Qiang Wang, Xintian Jin, Jiajia Zhu, Mengzhu Wang, Xiyu Liu
Anti-Cancer Drugs.2015; 26(4): 388. CrossRef

Loss of PTEN Expression is an Independent Poor Prognostic Factor in Non-small Cell Lung Cancer.: Seol Bong Yoo, Xianhua Xu, Hyun Ju Lee, Sanghoon Jheon, Choon Taek Lee, Gheeyoung Choe, Jin Haeng Chung; Korean J Pathol. 2011;45(4):329-335.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.329

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Abstract PDF

BACKGROUND
Alterations in the phosphatase and tensin homolog (PTEN) are correlated with tumor progression. Downregulation of PTEN is related to drug resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the prognostic significance of PTEN in patients with NSCLC and its correlation with EGFR.
METHODS
Two hundred eighty eight surgically resected NSCLC samples, including 168 adenocarcinomas (ADCs), 99 squamous cell carcinomas (SCCs) and 21 other NSCLCs were analyzed for the PTEN. The results were correlated with other clinicopathological variables including EGFR amplification and mutation.
RESULTS
Loss of PTEN was detected in 42.4% of NSCLCs, specifically 28.6% of ADCs, 66.7% of SCCs, and 38.1% of others. Loss of PTEN was significantly associated with SCC, smoking, male gender, and higher stage. In a multivariate analysis, loss of PTEN was significantly associated with short progression-free survival (p=0.037). No association between PTEN and EGFR was observed.
CONCLUSIONS
These results suggest that loss of PTEN results in shorter progression-free survival in patients with NSCLC, and loss of PTEN is more associated with SCC, smoking, male gender, and higher T stage by the 7th tumor, node and metastasis staging system but not EGFR status.

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Molecular mechanisms underlying the regulation of tumour suppressor genes in lung cancer
Jia Yee Lee, Richie R. Bhandare, Sai H.S. Boddu, Afzal B. Shaik, Lakshmana Prabu Saktivel, Gaurav Gupta, Poonam Negi, Muna Barakat, Sachin Kumar Singh, Kamal Dua, Dinesh Kumar Chellappan
Biomedicine & Pharmacotherapy.2024; 173: 116275. CrossRef
Alterations in the PI3K Pathway Drive Resistance to MET Inhibitors in NSCLC Harboring MET Exon 14 Skipping Mutations
Philippe Jamme, Marie Fernandes, Marie-Christine Copin, Clotilde Descarpentries, Fabienne Escande, Angela Morabito, Valérie Grégoire, Matthieu Jamme, Simon Baldacci, David Tulasne, Zoulika Kherrouche, Alexis B. Cortot
Journal of Thoracic Oncology.2020; 15(5): 741. CrossRef
PTEN Tumor-Suppressor: The Dam of Stemness in Cancer
Francesca Luongo, Francesca Colonna, Federica Calapà, Sara Vitale, Micol E. Fiori, Ruggero De Maria
Cancers.2019; 11(8): 1076. CrossRef
PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around
Anastasios Gkountakos, Giulia Sartori, Italia Falcone, Geny Piro, Ludovica Ciuffreda, Carmine Carbone, Giampaolo Tortora, Aldo Scarpa, Emilio Bria, Michele Milella, Rafael Rosell, Vincenzo Corbo, Sara Pilotto
Cancers.2019; 11(8): 1141. CrossRef
PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature
Jian Xiao, Cheng-Ping Hu, Bi-Xiu He, Xi Chen, Xiao-Xiao Lu, Ming-Xuan Xie, Wei Li, Shu-Ya He, Shao-Jin You, Qiong Chen
Oncotarget.2016; 7(36): 57832. CrossRef
Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment
Seol Bong Yoo, Yu Jung Kim, Hyojin Kim, Yan Jin, Ping-Li Sun, Sanghoon Jheon, Jong Seok Lee, Jin-Haeng Chung
Annals of Surgical Oncology.2013; 20(S3): 545. CrossRef
High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas
Ping‐Li Sun, Yan Jin, Hyojin Kim, Choon‐Taek Lee, Sanghoon Jheon, Jin‐Haeng Chung
Cancer Cytopathology.2013; 121(6): 311. CrossRef
Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior
Ioannis Panagiotou, Stavros N. Georgiannos, Evangelos Tsiambas, Andreas Karameris, Marios Konstantinou, Andreas C. Lazaris, Nikolaos Kavantzas, George Vilaras, Efstratios Patsouris
Asian Pacific Journal of Cancer Prevention.2012; 13(12): 6311. CrossRef
Expression of the Mammalian Target of Rapamycin Pathway Markers in Lung Adenocarcinoma and Squamous Cell Carcinoma
Hyun-Soo Kim, Gou Young Kim, Sung-Jig Lim, Youn Wha Kim
Pathobiology.2012; 79(2): 84. CrossRef

p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors.: Seok Ju Park, Woo Jung Sung, Mi Jin Kim; Korean J Pathol. 2010;44(6):597-604.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.597

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Abstract PDF

BACKGROUND
At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated.
METHODS
A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed.
RESULTS
Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011).
CONCLUSIONS
High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

Citations

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Over-expression of β-catenin is associated with high grade of prostatic cancer in Libyan patients
W. Said, F. Emaetig, K. El Gehani, T. Eldarat, A. Buhmeida, N. Enattah, A. Elzagheid, O. Al-Fituri
African Journal of Urology.2017; 23(2): 133. CrossRef
Bcl2 en cáncer avanzado de próstata y asociación con resistencia a la castración
R.F. Velázquez-Macías, F.E. De La Torre-Rendón, G. Ramos-Rodríguez, C.A. Calzada-Mendoza, R.M. Coral-Vázquez
Revista Mexicana de Urología.2016; 76(5): 288. CrossRef
Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: A retrospective study from the view point of new 2010 anatomic stage/prognostic groups
Tae‐Jung Kim, Ji Youl Lee, Tae‐Kon Hwang, Chang Suk Kang, Yeong‐Jin Choi
Journal of Surgical Oncology.2011; 104(5): 472. CrossRef

Cell Mediated Immunity in Tubulointerstitial Nephritis of Rats.: Hyeon Joo Jeong; Korean J Pathol. 1995;29(5):634-643.

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Abstract: To investigate the tubular major histocompatibility complex(MHC) expression and inflammatory phenotypes in tubulointerstitial nephritis, Lewis rats were inununized with azobenzen-earsonate-tyrosine in complete Freund adjuvant and challenged either foot pad or kidney, either by subcapsular injection or by ex vivo perfusion. The rats were sacrificed 2, 3, 5, 10 and 15 days after antigenic challenge. Foot pad swelling was significant at the antigenic challenge site (151.8 vs 6.8 x 10(-2) mm) at 24 hours. Tubulointerstitial nephritis was induced by both methods and the inflammatory infiltrate which first appeared on day 2, became prominent at day 5, then gradually subsided in ex vivo perfused rats, while inflannnation started on day 3 in subcapsular injected rats. The major site of inflammation was in the cortex and outer stripe of the outer medulla, with predominance of mononuclear cells throughout the course. The inflammatory cells showed mainly OX8 and ED1 positivity with OX19, W3/25 and CD5 positivity in minority. RT1B expression was diffuse in the cytoplasm of proximal tubules at day 2 and 5. These results suggest the involvement of cell mediated immunity in this experimental model, and the possibility that tubular epidielial cells process antigen and then become targets in immune injury.

Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma.: Kwang Sun Suh, Young Ho Lee, Sun Young Na, Moon Il Park, Hun Soo Kim, Saeng Keum Lee; Korean J Pathol. 2005;39(5):313-319.

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Abstract PDF: BACKGROUND
Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas.
METHODS
Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN.
RESULTS
Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018).
CONCLUSIONS
Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.

Loss of PTEN Expression in Breast Cancers.: Sun Hee Chang, Shi Nae Lee, Min Sun Cho, Heasoo Koo, Woon Sup Han, Seock Ah Im, Byung In Moon, Hyun Suk Suh, Hye Young Choi, Sun Hee Sung; Korean J Pathol. 2005;39(4):236-241.

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Abstract PDF: Background
: PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression.
Results
: Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.

PTEN and p53 Mutations in Endometrial Carcinomas.: Jae Sung Choi, Kwang Sun Suh, Heung Tae Noh, Yun Ee Rhee, Sun Young Na, Hye Kyung Lee; Korean J Pathol. 2005;39(1):1-8.

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Abstract PDF: BACKGROUND
Endometrial carcinomas are pathogenetically classified into two major types; endometrioid carcinoma (EC) and serous carcinoma (SC). The most frequently altered gene in EC is the PTEN tumor suppressor gene (TSG). SC is usually associated with mutations in the p53 TSG.
METHODS
To further determine the role of PTEN and p53 mutation in endometrial carcinogenesis, the analysis of 33 endometrial carcinomas, including 28 ECs and 5 SCs, for loss of heterozygosity (LOH) on 10q23 and for mutation in all 9 coding exons of PTEN and the 5-8 exons of p53, using SSCP-PCR methods was carried out.
RESULTS
LOH was detected in at least one marker in 12 (54.5%) of 22 ECs, but in only one (20.0%) of 5 SCs. Somatic PTEN mutations were detected in 10 (35.7%) of 28 ECs. PTEN was altered in 67.9% of ECs and in 20.0% of SCs, including those with 10q23 LOH. No PTEN mutations were found among the SCs. Somatic p53 mutations were detected in 2 (7.1%) of 28 ECs and 3 (60.0%) of 5 SCs.
CONCLUSIONS
PTEN gene alterations contribute to the pathogenesis of an endometrioid subtype of endometrial carcinoma, but not to the serous type. In contrast, p53 plays an important role in the pathogenesis of SCs.

The Relationship between PTEN Tumor Suppressor Gene and Vascular Endothelial Growth Factor-Mediated Angiogenesis in Breast Cancer.: Jean Kyung Park, Min Jung Jung, Bong Kwon Chun, Bang Hur; Korean J Pathol. 2004;38(2):100-105.

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Abstract PDF: BACKGROUND
PTEN is a novel tumor suppressor gene located at chromosome 10q23.3. Loss of PTEN function has been implicated in the progression of several types of cancer. Angiogenesis is a critical factor in tumor growth and metastasis. We investigated PTEN expression in invasive breast cancers and described its role in the regulation of angiogenesis related to vascular endothelial growth factor (VEGF).
METHODS
Forty-five, surgically resected, formalin-fixed and paraffin embedded breast cancer tissue samples were analyzed for PTEN and VEGF expressions by immunohistochemistry and for microvessel density (MVD) by CD34 immunostaining.
RESULTS
Loss of PTEN expression was found in 35.6% (16/45) of the breast cancer tissues, all of which showed positive VEGF expression. Among 29 cases with normal PTEN expression, 15 (51.7%) were VEGF positive. MVD was significantly higher in tumors with a loss of PTEN expression than in those with normal PTEN expression.
CONCLUSION
A loss of PTEN expression might increase the VEGF-related angiogenesis in breast cancer. There was no correlation between PTEN expression and clinicopathologic parameters. Detection of the loss of PTEN expression may serve as a useful biologic marker for progression in invasive breast cancer.

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