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Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival

The retinoblastoma (Rb) pathway controls the G1-S checkpoint of the cell cycle. Inactivating mutations and deletions of p16 and Rb and up-regulation of cyclin D1 disrupt this pathway and occur in many cancers. However, the concurrent expression of these genes in primary and metastatic gastric cancer...

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Published in:Human pathology 2003-12, Vol.34 (12), p.1276-1282
Main Authors: Feakins, Roger M, Nickols, Carole D, Bidd, Heena, Walton, Sarah-Jane
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description The retinoblastoma (Rb) pathway controls the G1-S checkpoint of the cell cycle. Inactivating mutations and deletions of p16 and Rb and up-regulation of cyclin D1 disrupt this pathway and occur in many cancers. However, the concurrent expression of these genes in primary and metastatic gastric cancer is unknown, and the prognostic value of their expression is unclear. In this study, the expression of cyclin D1, retinoblastoma protein (pRb), and p16 in 67 resected gastric adenocarcinomas, and of pRb and p16 in 40 associated lymph node metastases, was determined using a streptavidin-biotin-peroxidase immunohistochemical method. Relationships with clinical and pathological features were analyzed. Cyclin D1 overexpression (≥5% expression) was seen in 55% of cancers; pRb loss (
doi_str_mv 10.1016/j.humpath.2003.07.005
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Inactivating mutations and deletions of p16 and Rb and up-regulation of cyclin D1 disrupt this pathway and occur in many cancers. However, the concurrent expression of these genes in primary and metastatic gastric cancer is unknown, and the prognostic value of their expression is unclear. In this study, the expression of cyclin D1, retinoblastoma protein (pRb), and p16 in 67 resected gastric adenocarcinomas, and of pRb and p16 in 40 associated lymph node metastases, was determined using a streptavidin-biotin-peroxidase immunohistochemical method. Relationships with clinical and pathological features were analyzed. Cyclin D1 overexpression (≥5% expression) was seen in 55% of cancers; pRb loss (&lt;20% expression), in 33%; p16 loss (&lt;10% expression), in 49%; and at least 1 of these abnormalities, in 92.5%. Cyclin D1 overexpression was associated with poor differentiation ( P = 0.027) and signet ring cell type ( P = 0.029). pRb expression was lower in lymph node metastases than in the corresponding primary tumors ( P &lt;0.001). Univariate and multivariate survival analysis (minimum follow-up 72 months or until death) revealed that &lt;20% pRb expression, &lt;30% pRb expression, and International Union Against Cancer stage &gt;2 were associated with worse overall survival. The results suggest that Rb pathway disturbances play an important role in gastric carcinogenesis. 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Inactivating mutations and deletions of p16 and Rb and up-regulation of cyclin D1 disrupt this pathway and occur in many cancers. However, the concurrent expression of these genes in primary and metastatic gastric cancer is unknown, and the prognostic value of their expression is unclear. In this study, the expression of cyclin D1, retinoblastoma protein (pRb), and p16 in 67 resected gastric adenocarcinomas, and of pRb and p16 in 40 associated lymph node metastases, was determined using a streptavidin-biotin-peroxidase immunohistochemical method. Relationships with clinical and pathological features were analyzed. Cyclin D1 overexpression (≥5% expression) was seen in 55% of cancers; pRb loss (&lt;20% expression), in 33%; p16 loss (&lt;10% expression), in 49%; and at least 1 of these abnormalities, in 92.5%. Cyclin D1 overexpression was associated with poor differentiation ( P = 0.027) and signet ring cell type ( P = 0.029). pRb expression was lower in lymph node metastases than in the corresponding primary tumors ( P &lt;0.001). Univariate and multivariate survival analysis (minimum follow-up 72 months or until death) revealed that &lt;20% pRb expression, &lt;30% pRb expression, and International Union Against Cancer stage &gt;2 were associated with worse overall survival. The results suggest that Rb pathway disturbances play an important role in gastric carcinogenesis. The poor prognosis of cancers with low pRb expression and the reduced pRb expression in lymph node metastases raise the possibility that Rb and related genes also influence progression.</description><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biotechnology</subject><subject>Breast cancer</subject><subject>Cell cycle</subject><subject>cyclin D1</subject><subject>Cyclin D1 - biosynthesis</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis</subject><subject>Cyclin-dependent kinases</subject><subject>Female</subject><subject>gastric carcinoma</subject><subject>Gastroenterology. Liver. Pancreas. 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Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Lymphatic Metastasis - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Multivariate analysis</topic><topic>p16</topic><topic>Pathogenesis</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>retinoblastoma protein</topic><topic>Retinoblastoma Protein - biosynthesis</topic><topic>Stomach Neoplasms - mortality</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Studies</topic><topic>Survival analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feakins, Roger M</creatorcontrib><creatorcontrib>Nickols, Carole D</creatorcontrib><creatorcontrib>Bidd, Heena</creatorcontrib><creatorcontrib>Walton, Sarah-Jane</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feakins, Roger M</au><au>Nickols, Carole D</au><au>Bidd, Heena</au><au>Walton, Sarah-Jane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2003-12-01</date><risdate>2003</risdate><volume>34</volume><issue>12</issue><spage>1276</spage><epage>1282</epage><pages>1276-1282</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><coden>HPCQA4</coden><abstract>The retinoblastoma (Rb) pathway controls the G1-S checkpoint of the cell cycle. Inactivating mutations and deletions of p16 and Rb and up-regulation of cyclin D1 disrupt this pathway and occur in many cancers. However, the concurrent expression of these genes in primary and metastatic gastric cancer is unknown, and the prognostic value of their expression is unclear. In this study, the expression of cyclin D1, retinoblastoma protein (pRb), and p16 in 67 resected gastric adenocarcinomas, and of pRb and p16 in 40 associated lymph node metastases, was determined using a streptavidin-biotin-peroxidase immunohistochemical method. Relationships with clinical and pathological features were analyzed. Cyclin D1 overexpression (≥5% expression) was seen in 55% of cancers; pRb loss (&lt;20% expression), in 33%; p16 loss (&lt;10% expression), in 49%; and at least 1 of these abnormalities, in 92.5%. Cyclin D1 overexpression was associated with poor differentiation ( P = 0.027) and signet ring cell type ( P = 0.029). pRb expression was lower in lymph node metastases than in the corresponding primary tumors ( P &lt;0.001). Univariate and multivariate survival analysis (minimum follow-up 72 months or until death) revealed that &lt;20% pRb expression, &lt;30% pRb expression, and International Union Against Cancer stage &gt;2 were associated with worse overall survival. The results suggest that Rb pathway disturbances play an important role in gastric carcinogenesis. The poor prognosis of cancers with low pRb expression and the reduced pRb expression in lymph node metastases raise the possibility that Rb and related genes also influence progression.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>14691913</pmid><doi>10.1016/j.humpath.2003.07.005</doi><tpages>7</tpages></addata></record>
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subjects Adenocarcinoma - mortality
Adenocarcinoma - pathology
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Biomarkers, Tumor - analysis
Biotechnology
Breast cancer
Cell cycle
cyclin D1
Cyclin D1 - biosynthesis
Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis
Cyclin-dependent kinases
Female
gastric carcinoma
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Lymphatic Metastasis - pathology
Male
Medical sciences
Middle Aged
Mortality
Multivariate analysis
p16
Pathogenesis
Prognosis
Proteins
retinoblastoma protein
Retinoblastoma Protein - biosynthesis
Stomach Neoplasms - mortality
Stomach Neoplasms - pathology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Studies
Survival analysis
Tumors
title Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival
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