| 1. |
- Lindmark, G, et al.
(författare)
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Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer : relation to survival.
- 1993
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 19:1, s. 50-60
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Tidskriftsartikel (refereegranskat)abstract
- The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.
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| 2. |
- Lindmark, G, et al.
(författare)
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Prognostic predictors in colorectal cancer.
- 1994
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 37:12, s. 1219-27
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Better prognostic predictors in colorectal cancer than the Dukes stage are necessary for individualized therapy and follow-up.METHODS: Survival among 212 patients operated on for colorectal cancer was examined regarding various clinical, histopathologic, cellular, and serologic tumor characteristics.RESULTS: Beside the Dukes stage, which was the most powerful variable, the erythrocyte sedimentation rate, leukocyte blood count, alkaline phosphatase, aspartate aminotransferase, six different serum tumor markers, number of small blood vessels, and age were found to be significantly associated with survival. The leukocyte blood count, alkaline phosphatase, and aspartate aminotransferase retained their significance in a multivariate model including tumor differentiation, local tumor stage, and age. Inclusion of tissue polypeptide antigen, the most powerful tumor marker in the multivariate model, showed that only the tumor stage, tissue polypeptide antigen, and age were statistically significantly correlated to survival. This was valid both for the group of patients considered as potentially curable and for those who potentially have been cured (Dukes Stages A-C).CONCLUSIONS: A great number of prognostic predictors failed to discard Dukes stage as the best one. One serum tumor marker, tissue polypeptide antigen, contains independent additional prognostic information.
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| 3. |
- Lindmark, G, et al.
(författare)
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Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer.
- 1993
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Ingår i: Laboratory Investigation. - 0023-6837 .- 1530-0307. ; 69:6, s. 682-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear.EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively.RESULTS: All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome.CONCLUSIONS: The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.
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| 4. |
- Sundberg, Christian, et al.
(författare)
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Microvascular pericytes express platelet-derived growth factor-beta receptors in human healing wounds and colorectal adenocarcinoma
- 1993
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Ingår i: American Journal of Pathology. - 0002-9440 .- 1525-2191. ; 143:5, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- The expression of platelet-derived growth factor- beta (PDGF-beta) receptors in the microvasculature of human healing wounds and colorectal adenocarcinoma was investigated. Frozen sections were subjected to double immunofluorescence staining using monoclonal antibodies (MAbs) specific for pericytes (MAb 225.28 recognizing the high-molecular weight-melanoma-associated antigen, expressed by activated pericytes during angiogenesis), endothelial cells (MAb PAL-E), laminin, as well as PDGF-beta receptors (MAb PDGFR-B2) and its ligand PDGF-B chain (MAb PDGF 007). Stained sections were analyzed by computer-aided imaging processing that allowed for a numerical quantification of the degree of colocalization of the investigated antigens. An apparent background colocalization, varying between 23 and 35%, between markers for cells not expected to co-localize was recorded. This background could be due to limitations of camera resolution, to out-of-focus fluorescence, and to interdigitations of the investigated structures. In all six tumor specimens, co-localization of PDGF-beta receptors and PAL-E was not different from the background co-localization, whereas that of PDGF-beta receptors and high-molecular weight-melanoma-associated antigen was significantly higher with mean values between 57 and 71%. Qualitatively, the same pattern was obtained in the two investigated healing wounds. PDGF-B chain did not co-localize with either PAL-E or high-molecular weight-melanoma-associated antigen, but PDGF-B chain-expressing cells were, however, frequently found juxtaposed to the microvasculature. The expression of PDGF-beta receptors on pericytes in activated microvessels and the presence of PDGF-B chain-expressing cells in close proximity to the microvasculature of healing wounds and colorectal adenocarcinoma is compatible with a role for PDGF in the physiology of the microvasculature in these conditions.
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