Indicators for Treatment Strategies of Colorectal Liver Metastases

Ueno, Hideki; Mochizuki, Hidetaka; Hatsuse, Kazuo; Hase, Kazuo; Yamamoto, Tetsuhisa

doi:10.1097/00000658-200001000-00009

Cited by 147 publications

(140 citation statements)

References 28 publications

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“…Tumor budding is defined as the presence of isolated single cells or small cell clusters (up to 4) scattered in the stroma at the invasive tumor margin and is established as an adverse prognostic indicator. [28][29][30][31][32][33] Tumor budding is at least in part driven by the wnt signaling pathway as attested by the fact that nuclear b-catenin accumulates in the nuclei in tumor buds (dedifferentiated cancer cells) at the invasive tumor border. [34][35][36][37] In the present study, nuclear pERK expression was correlated with increasing RHAMM expression in MMR proficient (P ¼ 0.012) and with complete RHAMM expression in presumed Lynch syndrome (P ¼ 0.03), whereas an association was not found in MLH1-negative CRC.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

et al. 2006

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RHAMM, a member of the microtubule-associated protein family that interacts with the mitogen-activated protein kinase pathway, is associated with tumor progression, aggressive disease and shortened survival in several tumor types. This study aimed to determine the prognostic value of RHAMM in colorectal cancer (CRC). A series of 1420 unselected, nonconsecutive CRC resections were subdivided into three groups: (1) DNA mismatch repair (MMR)-proficient, (2) MLH1 negative and (3) presumed Lynch syndrome. Immunohistochemical analysis of RHAMM expression (0 vs 40%), increasing expression (increasing percentage positivity) and complete expression (100 vs o100%) was performed using tissue microarray technique and the results were correlated with clinicopathological parameters. Fifty-seven tissue samples of normal colonic mucosa were included as a control group. In a univariate analysis increasing and complete expression of RHAMM were associated with higher N stage (P ¼ 0.023 and 0.021) and worse survival (Po0.0001) in MMR-proficient CRC. Complete expression of RHAMM was associated with worse survival in presumed Lynch syndrome (P ¼ 0.016). In MLH1-negative CRC there was no association between RHAMM expression and the clinicopathological features. In a multivariate analysis, increasing RHAMM expression was an independent adverse prognostic factor in MMR-proficient CRC (Po0.0001) and complete expression in MMR-proficient CRC and presumed Lynch syndrome (Po0.0001 and P ¼ 0.031, respectively). Nuclear pERK expression was associated with increasing RHAMM expression in MMR-proficient CRC (P ¼ 0.012) and with complete RHAMM expression in presumed HNPCC (P ¼ 0.03). Increasing and complete RHAMM expressions are independent adverse prognostic factors in MMR-proficient CRC and presumed Lynch syndrome.

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Section: Discussionmentioning

confidence: 99%

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

et al. 2006

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“…The grade of 'tumor budding' has also been shown to be a powerful prognostic factor for patients with postoperative liver recurrence as well as patients with primary CRC. 36 Because of our favorable interobserver agreement for the judgment of LN-5g2 expression, its evaluation was indicated to be useful as an objective marker of tumor cell dedifferentiation at the invasive front of CRC in a clinicopathological setting.…”

Section: Comparison Of Incidence and Prognostic Implication Of Ln-5c2mentioning

confidence: 99%

Prognostic implication of laminin-5 gamma 2 chain expression in the invasive front of colorectal cancers, disclosed by area-specific four-point tissue microarrays

Shinto

Tsuda

Ueno

et al. 2005

Laboratory Investigation

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The laminin-5 gamma 2 chain (LN-5c2) is known to be a marker of invasion in several cancer types. Our purpose was to examine the prognostic significance of LN-5c2 expression in different areas of individual colorectal cancers (CRCs) by using tissue microarrays (TMAs), and to clarify the optimal areas for prognostic assessment. Using formalin-fixed paraffin-embedded tissue blocks of pT3 primary CRCs resected from 120 patients, we constructed TMA blocks of tissue core specimens taken from the submucosal invasive front, subserosal invasive front, central area, and rolled edge of each tumor. Using these four-point TMA sets, cytoplasmic LN-5c2 expression was immunohistochemically surveyed, and the area-specific prognostic significance of LN-5c2 expression was evaluated. The data revealed that 35, 30, 15 and 10% of the 120 CRCs showed highgrade LN-5c2 expression in the submucosal invasive front, subserosal invasive front, central area and rolled edge, respectively. Disease-specific survival curves for the groups with high-and low-grade LN-5c2 in the submucosal invasive front and subserosal invasive front were different significantly or of marginal difference (respective 5-year survival rates: 54 and 78% for submucosal invasive front (P ¼ 0.030) and 58 and 75% for subserosal invasive front (P ¼ 0.055)). Multivariate analysis revealed that the grades of LN-5c2 expression in submucosal invasive front (hazard ratio ¼ 2.0, P ¼ 0.047) and subserosal invasive front (hazard ratio ¼ 2.9, P ¼ 0.0033) were independent prognostic factors. In contrast, the grades of LN-5c2 expression in the central area and rolled edge did not have a significant impact on patient prognosis. Analysis using area-specific fourpoint TMAs clearly demonstrated that LN-5c2 expression in the invasive front largely influences the degree of clinical aggressiveness of CRC and its tendency to metastasize.

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“…The metastatic activity or prognostic outcome in colorectal cancer has been reported to be associated with morphologic features at the invasive front of the primary tumor. These morphologic features are called tumor ''budding'' (2,3) or tumor ''focal dedifferentiation'' (4,5).…”

mentioning

confidence: 99%

Identification of the Molecular Mechanisms for Dedifferentiation at the Invasion Front of Colorectal Cancer by a Gene Expression Analysis

Oku

Sawada²,

Takifuji³

et al. 2008

Clinical Cancer Research

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Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer. Experimental Design: Two types of colorectal cancer were selected. Both types were welldifferentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (typeA, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers. Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-h,Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification. Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-h, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

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Indicators for Treatment Strategies of Colorectal Liver Metastases

Cited by 147 publications

References 28 publications

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

Prognostic implication of laminin-5 gamma 2 chain expression in the invasive front of colorectal cancers, disclosed by area-specific four-point tissue microarrays

Identification of the Molecular Mechanisms for Dedifferentiation at the Invasion Front of Colorectal Cancer by a Gene Expression Analysis

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