{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:29:22Z","timestamp":1774085362955,"version":"3.50.1"},"reference-count":82,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11]]},"abstract":"\n Context.<\/jats:italic>\n \u2014Phosphatase and tensin homolog (\n PTEN<\/jats:italic>\n ) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of\n PTEN<\/jats:italic>\n occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma.\n <\/jats:p>\n \n Objective.<\/jats:italic>\n \u2014To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA).\n <\/jats:p>\n \n Design.<\/jats:italic>\n \u2014We constructed tissue microarrays by using archival tissue from 92 patients (55 males, 37 females; median age, 63 years; age range, 37 to 87 years) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. PTEN expression was evaluated by immunohistochemistry, scored semiquantitatively (based on staining intensity and percentage positive tumor cells), and correlated with clinicopathologic features and survival.\n <\/jats:p>\n \n Results.<\/jats:italic>\n \u2014Of 92 cases, 23 (25.0%) were PTEN negative. Loss of PTEN expression correlated with lymph node metastasis (\n P<\/jats:italic>\n = .004), advanced American Joint Committee on Cancer (AJCC) stage (\n P<\/jats:italic>\n = .02), and higher frequency of recurrence (\n P<\/jats:italic>\n = .03). Patients with PTEN-negative tumors had shorter disease-free survival (DFS, mean: 89.0 \u00b1 20.8 months) and overall survival (OS, mean: 93.1 \u00b1 19.1 months) than those with PTEN-positive tumors (DFS, mean: 161.4 \u00b1 11.7 months,\n P<\/jats:italic>\n = .01; OS, mean: 175.4 \u00b1 11.0 months,\n P<\/jats:italic>\n = .001). In multivariate analyses, PTEN expression was a prognostic factor for both DFS and OS, independent of AJCC stage, lymph node status, pathologic tumor (pT) stage, and differentiation.\n <\/jats:p>\n \n Conclusions.<\/jats:italic>\n \u2014Loss of PTEN expression is associated with poor DFS and OS in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA.\n <\/jats:p>","DOI":"10.5858\/arpa.2012-0418-oa","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T08:55:38Z","timestamp":1383123338000},"page":"1619-1626","source":"Crossref","is-referenced-by-count":14,"title":["The Expression of PTEN Is Associated With Improved Prognosis in Patients With Ampullary Adenocarcinoma After Pancreaticoduodenectomy"],"prefix":"10.5858","volume":"137","author":[{"given":"Stuti","family":"Shroff","sequence":"first","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Overman","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asif","family":"Rashid","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachna T.","family":"Shroff","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyali","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew H.","family":"Katz","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Wolff","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L.","family":"Abbruzzese","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason B.","family":"Fleming","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huamin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3906","reference":[{"issue":"3","key":"i1543-2165-137-11-1619-b01","series-title":"Curr Opin Gastroenterol","first-page":"280","article-title":"Ampullary cancer","volume":"26","author":"Heinrich\n S,","year":"2010","unstructured":"Heinrich\n S, \n \n Clavien\n PA. \n \n Ampullary cancer. 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Nat Rev Cancer. 2011;11(4):289\u2013301."},{"issue":"17","key":"i1543-2165-137-11-1619-b10","series-title":"Clin Cancer Res","first-page":"4325","article-title":"PI(3)king apart PTEN's role in cancer","volume":"16","author":"Zhang\n S,","year":"2010","unstructured":"Zhang\n S, \n \n Yu\n D. \n \n PI(3)king apart PTEN's role in cancer. Clin Cancer Res. 2010;16(17):4325\u20134330."},{"issue":"2","key":"i1543-2165-137-11-1619-b11","series-title":"Eur J Surg Oncol","first-page":"140","article-title":"Clinical significance of tumor suppressor PTEN in colorectal carcinoma","volume":"37","author":"Hsu\n CP,","year":"2011","unstructured":"Hsu\n CP, \n \n Kao\n TY, \n \n Chang\n WL, \n \n Nieh\n S, \n \n Wang\n HL, \n \n Chung\n YC. \n \n Clinical significance of tumor suppressor PTEN in colorectal carcinoma. Eur J Surg Oncol. 2011;37(2):140\u2013147."},{"issue":"2","key":"i1543-2165-137-11-1619-b12","series-title":"Histopathology","first-page":"229","article-title":"Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma","volume":"56","author":"Jang\n KS,","year":"2010","unstructured":"Jang\n KS, \n \n Song\n YS, \n \n Jang\n SH, \n et al\n . Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma. Histopathology. 2010;56(2):229\u2013239."},{"issue":"35","key":"i1543-2165-137-11-1619-b13","series-title":"J Clin Oncol","first-page":"5924","article-title":"Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer","volume":"27","author":"Laurent-Puig\n P,","year":"2009","unstructured":"Laurent-Puig\n P, \n \n Cayre\n A, \n \n Manceau\n G, \n et al\n . Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009;27(35):5924\u20135930."},{"issue":"1","key":"i1543-2165-137-11-1619-b14","series-title":"Mod Pathol","first-page":"131","article-title":"The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas","volume":"25","author":"Lee\n D,","year":"2012","unstructured":"Lee\n D, \n \n Do\n IG, \n \n Choi\n K, \n et al\n . The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas. 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Anticancer Res. 2002;22(3):1529\u20131536."},{"issue":"1","key":"i1543-2165-137-11-1619-b18","series-title":"Brain Pathol","first-page":"95","article-title":"Tissue microarrays: applications in neuropathology research, diagnosis, and education","volume":"12","author":"Wang\n H,","year":"2002","unstructured":"Wang\n H, \n \n Wang\n H, \n \n Zhang\n W, \n \n Fuller\n GN. \n \n Tissue microarrays: applications in neuropathology research, diagnosis, and education. Brain Pathol. 2002;12(1):95\u2013107."},{"issue":"1","key":"i1543-2165-137-11-1619-b19","series-title":"Cancer","first-page":"268","article-title":"Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation","volume":"118","author":"Estrella\n JS,","year":"2012","unstructured":"Estrella\n JS, \n \n Rashid\n A, \n \n Fleming\n JB, \n et al\n . Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation. Cancer. 2012;118(1):268\u2013277."},{"issue":"22","key":"i1543-2165-137-11-1619-b20","series-title":"J Natl Cancer Inst","first-page":"1922","article-title":"Mutational spectra of PTEN\/MMAC1 gene: a tumor suppressor with lipid phosphatase activity","volume":"91","author":"Ali\n IU,","year":"1999","unstructured":"Ali\n IU, \n \n Schriml\n LM, \n \n Dean\n M. \n \n Mutational spectra of PTEN\/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst. 1999;91(22):1922\u20131932."},{"issue":"3","key":"i1543-2165-137-11-1619-b21","series-title":"Cell","first-page":"403","article-title":"Tenets of PTEN tumor suppression","volume":"133","author":"Salmena\n L,","year":"2008","unstructured":"Salmena\n L, \n \n Carracedo\n A, \n \n Pandolfi\n PP. \n \n Tenets of PTEN tumor suppression. Cell. 2008;133(3):403\u2013414."},{"issue":"41","key":"i1543-2165-137-11-1619-b22","series-title":"Oncogene","first-page":"5443","article-title":"PTEN: a new guardian of the genome","volume":"27","author":"Yin\n Y,","year":"2008","unstructured":"Yin\n Y, \n \n Shen\n WH. \n \n PTEN: a new guardian of the genome. Oncogene. 2008;27(41):5443\u20135453."},{"issue":"11\u201312","key":"i1543-2165-137-11-1619-b23","series-title":"Clin Chim Acta","first-page":"846","article-title":"MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC)","volume":"411","author":"Zhang\n JG,","year":"2010","unstructured":"Zhang\n JG, \n \n Wang\n JJ, \n \n Zhao\n F, \n \n Liu\n Q, \n \n Jiang\n K, \n \n Yang\n GH. \n \n MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). 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Genes Chromosomes Cancer. 2004;41(2):117\u2013124."},{"issue":"2","key":"i1543-2165-137-11-1619-b26","series-title":"Gynecol Oncol","first-page":"307","article-title":"PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas","volume":"112","author":"Ho\n CM,","year":"2009","unstructured":"Ho\n CM, \n \n Lin\n MC, \n \n Huang\n SH, \n et al\n . PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas. Gynecol Oncol. 2009;112(2):307\u2013313."},{"issue":"3","key":"i1543-2165-137-11-1619-b27","series-title":"Lab Invest","first-page":"285","article-title":"Promoter methylation and silencing of PTEN in gastric carcinoma","volume":"82","author":"Kang\n YH,","year":"2002","unstructured":"Kang\n YH, \n \n Lee\n HS, \n \n Kim\n WH. \n \n Promoter methylation and silencing of PTEN in gastric carcinoma. Lab Invest. 2002;82(3):285\u2013291."},{"issue":"9","key":"i1543-2165-137-11-1619-b28","series-title":"Cancer Biol Ther","first-page":"1321","article-title":"PTEN signaling pathways in glioblastoma","volume":"7","author":"Koul\n D.","year":"2008","unstructured":"Koul\n D. \n \n PTEN signaling pathways in glioblastoma. Cancer Biol Ther. 2008;7(9):1321\u20131325."},{"issue":"1","key":"i1543-2165-137-11-1619-b29","series-title":"Int J Cancer","first-page":"22","article-title":"PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma","volume":"91","author":"Salvesen\n HB,","year":"2001","unstructured":"Salvesen\n HB, \n \n MacDonald\n N, \n \n Ryan\n A, \n et al\n . PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int J Cancer. 2001;91(1):22\u201326."},{"issue":"5","key":"i1543-2165-137-11-1619-b30","series-title":"Clin Cancer Res","first-page":"1178","article-title":"Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation","volume":"8","author":"Soria\n JC,","year":"2002","unstructured":"Soria\n JC, \n \n Lee\n HY, \n \n Lee\n JI, \n et al\n . Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation. Clin Cancer Res. 2002;8(5):1178\u20131184."},{"issue":"11","key":"i1543-2165-137-11-1619-b31","series-title":"Genes Dev","first-page":"1327","article-title":"The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo","volume":"23","author":"Huse\n JT,","year":"2009","unstructured":"Huse\n JT, \n \n Brennan\n C, \n \n Hambardzumyan\n D, \n et al\n . The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev. 2009;23(11):1327\u20131337."},{"issue":"117","key":"i1543-2165-137-11-1619-b32","series-title":"Sci Signal","article-title":"Identification of the miR-106b\u223c25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation","volume":"3","author":"Poliseno\n L,","year":"2010","unstructured":"Poliseno\n L, \n \n Salmena\n L, \n \n Riccardi\n L, \n et al\n . Identification of the miR-106b\u223c25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal. 2010;3(117):ra29."},{"issue":"10","key":"i1543-2165-137-11-1619-b33","series-title":"J Clin Oncol","first-page":"1878","article-title":"RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer","volume":"22","author":"Bepler\n G,","year":"2004","unstructured":"Bepler\n G, \n \n Sharma\n S, \n \n Cantor\n A, \n et al\n . RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol. 2004;22(10):1878\u20131885."},{"issue":"6","key":"i1543-2165-137-11-1619-b34","series-title":"Tumori","first-page":"513","article-title":"Potential prognostic significance of p185(HER2) overexpression with loss of PTEN expression in gastric carcinomas","volume":"91","author":"Im\n SA,","year":"2005","unstructured":"Im\n SA, \n \n Lee\n KE, \n \n Nam\n E, \n et al\n . Potential prognostic significance of p185(HER2) overexpression with loss of PTEN expression in gastric carcinomas. 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