Investigation of the prognostic value of coexpressed erbB family members for the survival of colorectal cancer patients after curative surgery

Lee, Jenq‐Chang; Wang, Shan‐Tair; Chow, Nan‐Haw; Hb, Yang

doi:10.1016/s0959-8049(02)00004-7

Cited by 100 publications

(70 citation statements)

References 29 publications

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“…Notably, these trends were not present in the entire cohort, with the exception of EGFR variation by grade, consistent with previous results (11). This lack of EGFR correlation with stage and grade has been also reported by other authors (9,14,22), whereas inconsistent findings are presented among studies suggesting such connections (10,12,13). Therefore, a separate investigation of proximal and distal CRC appears to be necessary for a more accurate determination of the effect of EGFR status on the progression, aggressiveness and, probably, the outcome of the disease.…”

Section: ------------------------------------------------------------supporting

confidence: 92%

“…However, despite the modest size of our sample, our results were similar to those of several relevant studies (9,10,(12)(13)(14)22). Although we confirmed these results in the expanded additional subsets [created by combining stage and grade: interrelated features differentially representing tumor growth potential (34)], further investigation in a larger sample is necessary.…”

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confidence: 88%

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The pattern of epidermal growth factor receptor variation with disease progression and aggressiveness in colorectal cancer depends on tumor location

et al. 2012

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Abstract. The role of epidermal growth factor receptor (EGFR) in colorectal cancer (CRC) prognosis remains unclear despite the recent development of anti-EGFR treatments for metastatic disease. The heterogeneity of CRC may account for this discrepancy; proximal and distal CRC has been found to be genetically and clinicopathologically different. The aim of this study was to investigate the effect of tumor location on the association of EGFR with the conventional prognostic indicators (stage and grade) in CRC. Immunohistochemical assessment of EGFR was retrospectively performed in 119 primary CRC specimens and data were correlated with tumor stage and grade in the proximal and distal tumor subset. The molecular combination of EGFR with p53 (previously assessed in this sample) was similarly analyzed. EGFR positivity was detected in 34, 30 and 35% of the entire cohort, proximal and distal tumors, respectively. The pattern of EGFR clinicopathological correlation was found to differ by site. A reduction in the frequency of EGFR(+) with progression of stage and/or worsening of grade was observed proximally, whereas an opposite trend was recorded distally. Proximal tumors with stage I or with indolent features (stage I, welldifferentiated) exhibited a significantly higher proportion of EGFR positivity than other tumors of this location (p=0.023 and p=0.022, respectively) or corresponding distal tumors (p=0.018 and p=0.035, respectively). Moreover, the co-existence of EGFR and high p53 staining (accounting for 11% of cases) was found in a significantly higher proportion of stage IV tumors compared to other stages (p=0.004), although only for the distal subset. Proximal and distal tumors showed various patterns of EGFR variation with disease progression and aggressiveness. This disparity provides further support to the hypothesis that these particular subsets of CRC are distinct tumor entities. It may also be suggestive of a potentially different therapeutic approach according to tumor site, particularly regarding anti-EGFR targeted treatment. IntroductionColorectal cancer (CRC) is one of the most common malignancies and remains a major cause of cancer mortality in the West (1). It is also a multi-pathway disease with disparate subgroups exhibiting distinct genetic and clinicopathological features, and probably different outcomes (2). This may be the main reason for the variability in treatment response observed among patients of the same disease stage. Therefore, a combination of the conventional TNM staging classification (at present, the major prognostic indicator) with certain molecular markers involved in CRC tumorigenesis, with verified prognostic and predictive impact, is one of the main objectives of research worldwide (3).Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein member of the tyrosine-kinase receptor family, encoded by the c-erB1 proto-oncogene and is considered as a major regulator of several distinct cellular pathways. Activation of EGFR promotes carcinogenesis, by increasing prol...

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confidence: 92%

Section: ------------------------------------------------------------supporting

confidence: 88%

The pattern of epidermal growth factor receptor variation with disease progression and aggressiveness in colorectal cancer depends on tumor location

et al. 2012

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“…324 Increased ERBB3 mRNA or protein is more common, detected in 34-90%. 320,[325][326][327][328][329][330] Association with poor clinical outcome was noted in one study 328 but not in several others. [329][330][331] In a recent and particularly complete investigation, 332 colonic adenomas expressed more cytoplasmic ERBB3 than did normal tissues or carcinomas, whereas nuclear staining was observed in 82% of normal, 54% of adenomas and 23% of carcinomas, all significant differences.…”

Section: Melanomasmentioning

confidence: 90%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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“…Ainsi, une surexpression de l'EGFR a été documentée dans de nombreuses néoplasies épithéliales, incluant les CCR (25 % à 77 % des cas selon les études et les techniques utilisées) [11]. Dans les CCR, cette surexpression a pu être associée à un pronostic défavorable, même si les données sont controversées [12][13][14][15][16]. Les mécanismes qui conduisent à une dérégulation de l'activité de l'EGFR dans les néoplasies épithéliales ne sont que partiellement connus et très probablement multiples : boucle autocrine ligand-récepteur et/ou altérations génomique (amplification, surexpression, mutations, délétions, réarrangements) induisant une activation constitutionnelle de la voie.…”

Section: Le Récepteur De L'egf (Epidermal Growth Factorunclassified

Cancer colorectaux métastatiques et thérapies ciblées anti-EGFR

Viret

Gonçalvès

2009

Med Sci (Paris)

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Investigation of the prognostic value of coexpressed erbB family members for the survival of colorectal cancer patients after curative surgery

Cited by 100 publications

References 29 publications

The pattern of epidermal growth factor receptor variation with disease progression and aggressiveness in colorectal cancer depends on tumor location

The pattern of epidermal growth factor receptor variation with disease progression and aggressiveness in colorectal cancer depends on tumor location

The ERBB3 receptor in cancer and cancer gene therapy

Cancer colorectaux métastatiques et thérapies ciblées anti-EGFR

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