Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer.

Halvorsen, Tore; Seim, E

doi:10.1136/jcp.42.2.162

Cited by 177 publications

(127 citation statements)

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“…[24][25][26][27][28][29][30][31][32][33] As in this study, MSI tumors have previously been reported to have a higher degree of T-cell infiltration than MSS tumors. [35][36][37] Yet the potential confounding effect of MSI screening status on the prognostic importance of T-cell infiltration has been considered in only a minority of reports, of which most, 32,36,[39][40][41]46,53,54 but not all, 30,55 found that the better prognosis associated with dense T-cell infiltration was independent of MSI screening status.…”

Section: Discussionsupporting

confidence: 59%

“…Presence of peri-and intratumoral inflammatory cells has consistently been associated with a better prognosis in colorectal cancer. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Many of these reports have been based on routine hematoxylin and eosin stained tissue sections, but an increasing number of studies have used immunohistochemical markers such as the pan T-cell marker CD3. CD3 is a cell surface protein associated with the T-cell receptor.…”

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confidence: 99%

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Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor

et al. 2011

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The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eightgene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score Z7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score r4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P ¼ 0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.

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Section: Discussionsupporting

confidence: 59%

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confidence: 99%

Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor

et al. 2011

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“…It has been reported that a well-marked desmoplastic stromal reaction is associated with a poorer prognosis (31). Expression of MMP-1 that is regulated by Ets-1 has been observed in areas of extracellular matrix remodeling both in physiological and pathological situations (32).…”

Section: Discussionmentioning

confidence: 99%

Expression of the ets-1 Proto-Oncogene in Human Colorectal Carcinoma

et al. 2001

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The proto-oncogene, ets-1, is a transcription factor known to control the expression of a number of genes involved in extracellular matrix remodeling and has been postulated to play a role in cell migration and tumor invasion. To elucidate the involvement of ets-1 in human colorectal carcinomas, we examined 41 cases of colorectal adenoma and 122 cases of colorectal carcinoma by immunohistochemistry and compared the degree of Ets-1 expression with the depth of carcinoma invasion. In adenomas, 12 of 41 cases (29.3%) showed immunopositivity for Ets-1. 12 of 27 cases (44.4%) of adenoma with high grade dysplasia showed immunopositivity for Ets-1. However, there was no positive case in low or moderate dysplasia of adenoma. In contrast, 103 of 122 cases (84.4%) of colorectal adenocarcinoma showed immunoreactivity for Ets-1 in the carcinoma cells themselves. We investigated the relationship between pathological features in colorectal carcinoma and Ets-1 immunoreactivity of the tumor cells. Among the 122 cases of invasive carcinomas, Ets-1 immunoreactivity was significantly correlated with the depth grading of tumor invasion (P < .0001), the presence of lymph node metastasis (P < .05), lymphatic invasion (P < .01) and venous invasion (P < .05). However, Ets-1 expression did not correlate with histological differentiation. In situ hybridization also confirmed the presence of ets-1 mRNA in colorectal carcinomas.

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“…The composition of tumours varies dramatically among patients and has previously been linked to differential survival in the breast (Baak et al, 1985), lung (Nakajima, 1991;Maeshima et al, 2002;das Neves Pereira et al, 2004), skin (Breuninger et al, 1997), prostate cancer (Yanagisawa et al, 2007) and CRC (Halvorsen and Seim, 1989;Shepherd et al, 1997;Sis et al, 2005;Ngan et al, 2007;Tsujino et al, 2007). Most of these studies demonstrate that a greater proportion of stroma or an exaggerated desmoplastic response is associated with poorer patient outcomes (Jass, 1986;Roncucci et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…In CRC, the number of stromal myofibroblasts , vimentin expression and degree of stromal desmoplasia (Halvorsen and Seim, 1989;Shepherd et al, 1997;Sis et al, 2005) have been associated with patient prognosis in the past. So far, only one study has suggested that the proportion of tumour cells in CRC may be important (Mesker et al, 2007).…”

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confidence: 99%

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

et al. 2010

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BACKGROUND: The proportion of epithelial and stromal cells in tumours is thought to have an important role in the progression of epithelial malignancy. We aimed to determine whether the relative proportion of tumour (PoT) was related to survival in colorectal cancer. METHODS: The PoT at the luminal surface was measured by point counting using virtual tissue sections in a series of 145 colorectal cancer cases. The relationship of PoT to clinicopathological parameters including cancer-specific survival was analysed. Modified receiver operating characteristic curves were used to determine the optimum cut off points to dichotomise the data for survival analyses. RESULTS: Tumours with PoT-low (p47%) were associated with significantly lower cancer-specific survival when compared to PoT-high (hazard ratio (HR) ¼ 2.087, 95% CI ¼ 1.088 -4.003, P ¼ 0.024). On sub-analysis, the prognostic effect remained significant in colonic tumours (HR ¼ 2.474, 95% CI ¼ 1.132 -5.408, P ¼ 0.019) and tumour, node, metastasis stage III disease (HR ¼ 3.480, 95% CI ¼ 0.325 -9.136, P ¼ 0.007). Multivariate Cox regression analysis demonstrated that PoT was an independent prognostic marker when adjusted for age, T stage, N stage and extramural vascular invasion (P ¼ 0.017). CONCLUSION: This study suggests that a low proportion of tumour cells in colorectal cancer is related to poor cancer-specific survival. A relatively quick, inexpensive and well-established method such as point counting on diagnostic tissue sections could be used to identify a subset of patients who may benefit from adjuvant therapy.

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Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer.

Cited by 177 publications

References 18 publications

Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor

Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor

Expression of the ets-1 Proto-Oncogene in Human Colorectal Carcinoma

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

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