Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Robson, Helen; Anderson, Elizabeth J.; James, Roger D; Schofield, Philip F.

doi:10.1038/bjc.1996.432

Cited by 97 publications

(60 citation statements)

References 33 publications

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“…Poorer survival was observed in patients with positive staining for TGF-β-1. This was more apparent for patients receiving a palliative resection of their primary tumour than for patients receiving a curative resection (Robson et al, 1996). Unfortunately, evaluation of the independence of TGF-β-1 staining from Dukes' stage was not reported in this study.…”

Section: Transforming Growth Factor (Tgf) α and β-1mentioning

confidence: 53%

“…Resistance to TGF-β-1-induced growth inhibition is observed in colorectal cancer and is associated with tumour progression in laboratory models (Robson et al, 1996). TGF-β-1 staining was evaluated in formalinfixed tissue from 72 patients with colorectal cancer (Dukes' stage A, 5; B, 33; C, 16; D, 18) (Robson et al, 1996). Positive expression was observed in 58% of tumours and was associated with Dukes' classification (Dukes' D, 72% vs Dukes' A, 40%; P < 0.05).…”

Section: Transforming Growth Factor (Tgf) α and β-1mentioning

confidence: 99%

“…TGF-β-1 inhibits the growth of epithelial cells but stimulates mesenchymal cell proliferation and cell migration. Resistance to TGF-β-1-induced growth inhibition is observed in colorectal cancer and is associated with tumour progression in laboratory models (Robson et al, 1996). TGF-β-1 staining was evaluated in formalinfixed tissue from 72 patients with colorectal cancer (Dukes' stage A, 5; B, 33; C, 16; D, 18) (Robson et al, 1996).…”

Section: Transforming Growth Factor (Tgf) α and β-1mentioning

confidence: 99%

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Tumour markers of prognosis in colorectal cancer

1998

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Section: Transforming Growth Factor (Tgf) α and β-1mentioning

confidence: 53%

Section: Transforming Growth Factor (Tgf) α and β-1mentioning

confidence: 99%

Section: Transforming Growth Factor (Tgf) α and β-1mentioning

confidence: 99%

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Tumour markers of prognosis in colorectal cancer

1998

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“…25 Alternatively, the production of immune-inhibitory cytokines, such as FAS-L, IL-10 or TGF-b may also explain the observed discrepancies in leukocyte infiltration. [26][27][28][29] Regarding the question as to which arm of the immune systems plays the most significant role in the antitumor effect, it is generally believed that the activation of tumor-specific, cytotoxic T cells plays a more prominent role than the leukocytes involved in innate immunity (eg NK cells). In the present study, we provided evidence that NK cells or NK-like T cells also play an important role.…”

Section: Discussionmentioning

confidence: 99%

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Menon

Rhijn

Morreau

et al. 2004

Laboratory Investigation

199

172

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The efficacy of tumor cell-immune cell interactions depends on a number of factors, for example, the expression of HLA-I on tumor cells, the type of immune cell, the accessibility of tumor cells for immune cells and the expression of immunogenic epitopes. We assessed infiltration of CD4 þ , CD8 þ , CD56 þ and CD57 þ cells in the tumor epithelium, tumor stroma and advancing tumor margin of 93 colorectal carcinomas and correlated this to clinicopathological parameters, the expression of HLA-A and HLA-B/C on tumor cells, the presence of a basal membrane (BM)-like structure surrounding tumor nodules and the presence of microsatellite instability/ mutator phenotype (absent MLH-1 expression). The median intraepithelial CD4 þ , CD8 þ , CD56 þ and CD57 þ cell infiltrations were 3, 23, 0 and 0 cells/mm 2 tumor, respectively. HLA-A/BC expression by tumor cells was normal in 28/43%, heterogeneous in 59/48% and absent in 13/9% of the cases. A BM-like structure surrounding the tumor nodules was absent, present and thick in 47, 38 and 15% of the cases. Six cases lost MLH1 expression. There was a positive correlation between leukocyte infiltration in the three compartments for CD4 þ , CD8 þ , CD56 þ (partly) and CD57 þ (all Po0.05) cell infiltration. Intraepithelial CD8 þ cell infiltration inversely correlated with HLA-A (P ¼ 0.04) and HLA-B/C expression (P ¼ 0.04). Intraepithelial CD57 þ cell infiltration inversely correlated with HLA-B/C expression (P ¼ 0.04). Moreover, intraepithelial infiltration of CD8 þ and CD57 þ cells was inversely correlated to the presence of a BM-like structure (P ¼ 0.003 and 0.04, respectively). Uni-and multivariate analyses showed that a lower tumor stage (P ¼ 0.004) and marked infiltration of CD8 þ (P ¼ 0.04) and CD57 þ cells (P ¼ 0.05) at the advancing tumor margin were independent prognostic factors for a longer diseasefree survival. Loss of MLH1 expression was correlated with a significantly higher intraepithelial CD8 þ and CD57 þ cell infiltration. We conclude that infiltration of CD8 þ and CD57 þ cells are important prognostic factors in colorectal cancer. However, their interaction with tumor cells is inversely correlated to the presence of HLA-I on tumor cells and a thick BM-like structure around tumor islets. Our data indicate that NK cells might play an important role in the immune surveillance in colorectal cancer patients.

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“…3 TGF-␤ potently inhibits the proliferation of many cell types, including cells of epithelial and hematopoietic origin. 4,5 Increased production of TGF-␤ by malignant cells 6 as well as resistance of tumor cells to TGF-␤ 7,8 are commonly observed in neoplastic diseases and seem to contribute to their progression. In hematological malignancies, TGF-␤ overproduction plays a role in AML M7.…”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of the tumor suppressor Smad2 in acute lymphoid and myeloid leukemia

Wieser¹,

Gruber²,

Rieder

et al. 1998

Leukemia

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Smad4 is a tumor suppressor that is inactivated in about 50% of pancreatic carcinomas. Mutations in this gene have also been found with variable, yet much lower frequency in other tumor types and were absent from a large number of samples from patients with hematological malignancies. Smad2 shows considerable sequence similarity with Smad4 and cooperates with it in the growth inhibitory TGF-␤ pathway. Smad2 mutations have been found in a fraction of colon carcinomas and have been shown to impair the function of the corresponding proteins. However, only a few other tumor types have been screened for Smad2 mutations so far. Therefore, we analyzed 50 primary tumor samples from patients with acute lymphoid or myeloid leukemia (ALL or AML) and five cell lines of hematopoietic origin for alterations in the Smad2 gene. None of the specimens tested carried mutations in the conserved MH1 or MH2 domains of Smad2.

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Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Cited by 97 publications

References 33 publications

Tumour markers of prognosis in colorectal cancer

Tumour markers of prognosis in colorectal cancer

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Mutational analysis of the tumor suppressor Smad2 in acute lymphoid and myeloid leukemia

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