S_nmary Syndecans are a family of cell-surface heparan sulphate proteoglycans which are involved in cell-matrix interactions and growth factor binding. Syndecan-1 binds basic fibroblast growth factor (bFGF) and several components of the extracellular matrix. Syndecan-l expression is induced dunng keratinocyte differentiation and reduced during the formation of squamous cell carinomas (SCCs). The purpose of this study was to examine the association of syndecan-l expression with prognostic factors and clinical outcome in SCC of the head and neck. Frozen sections of 29 primary SCCs were analysed for syndecan-l expression using immunohistochemical methods. Intermediate or strong staining for syndecan-l was associated with a smaler primary tumour size (P = 0.0005) and higher histological grade of differentiation (P = 0.006) than negative or weakly positive staining. In a univariate analysis, syndecan-l-positive tumours were associated with higher overall (P = 0.001) and recurrence-free survival (P = 0.003) than those tumours with no or little syndecan-l expression. The results suggest that syndecan-l could be an important prognostic factor of SCC of the head and neck. Further studies on the prognostic significance of syndecan-I expression in SCCs are warranted.
Collagenase-3 (MMP-13) is a human matrix metalloproteinase specifically expressed by invading tumor cells in squamous cell carcinomas (SCCs) of the head and neck. Here, we have further elucidated the role of MMP-13 in tumor invasion by examining its expression in invasive malignant tumors of the female genital tract. Using in situ hybridization, expression of MMP-13 mRNA was detected in 9 of 12 vulvar SCCs, primarily in tumor cells, but not in intact vulvar epithelium, in cervical SCCs (n = 12), or in endometrial (n = 11) or ovarian adenocarcinomas (n = 8). MMP-13 expression was especially abundant in vulvar carcinomas showing metastasis to lymph nodes and was associated with expression of membrane type 1 MMP by tumor cells and gelatinase-A (MMP-2) by stromal cells, as detected by immunohistochemistry. MMP-13 mRNAs were detected in 9 of 11 cell lines established from vulvar carcinomas and in 4 of 6 cell lines from cervical carcinomas, whereas endometrial (n = 10) and ovarian (n = 9) carcinoma cell lines were negative for MMP-13 mRNA. No correlation was detected between MMP-13 expression and p53 gene mutations in vulvar SCC cell lines. However, MMP-13 expression was detected in 5 of 6 vulvar and cervical SCC cell lines harboring HPV 16 or 68 DNA. These results show that MMP-13 is specifically expressed by malignantly transformed squamous epithelial cells, including vulvar SCC cells, and appears to serve as a marker for their invasive capacity.
The study population consisted of 125 males and 112 females. The mean age was 59 years (males 61 years, females 58 years). Follow-up was at least 5 years. The commonest tumor location was the parotid gland (n = 152; 64%), followed by the minor salivary glands (n =46; 19%), the submandibular gland (n =38; 16%) and the sublingual gland (n = 1; 0.4%). The most frequent histological types of SGC were adenoid cystic carcinoma (n =65; 27%), mucoepidermoid carcinoma (n =45; 19%) and acinic cell carcinoma (n =41; 17%). Surgery, either alone or in combination with other treatment modalities, was used in 209 cases (88%). Radiotherapy was given to 136 patients (57%), 13 of whom (5%) did not undergo surgery. The 5-year overall survival rate was 56.5%, and for stages I-IV it was 78%, 25%, 21% and 23%, respectively (p <0.001; log-rank test). Of the commonest tumor types, the best 5-year relative survival rate was for patients with acinic cell carcinoma (96%), followed by those with mucoepidermoid (79%) and adenoid cystic carcinoma (74%).
Thirteen patients with malignant head and neck tumors were studied before they were treated with (18F) fluorodeoxyglucose (FDG) imaging and DNA flow cytometry (FCM). The nuclear DNA content and the percentage of proliferative cells (S + G2/M) were compared with the FDG uptake; FDG was retained in the primary tumor and/or neck metastasis in all patients. The accumulation of FDG did not correlate with histologic grade of the tumors, but there was a clear correlation (r = 0.86, P less than 0.001) between the proportion of the cells in S + G2/M phases of the cell cycle and the intensity of FDG accumulation. The uptake of FDG by the tumor also correlated with the percentage of S-phase cells (r = 0.82, P less than 0.001). The result suggests that enhanced glucose metabolism, measured by FDG uptake, is associated with the proliferative activity of the tumor. Thus, imaging with FDG may offer a new method to assess the aggressiveness of human cancer growth in vivo.
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