Stromelysin-3 expression in early (pT1) carcinomas and pseudoinvasive lesions of the colorectum

Abstract

Pseudoinvasion in colorectal adenomas is often difficult to distinguish from invasive carcinoma. Previous studies have indicated that expression of stromelysin-3 (ST-3), one of the metalloproteinase family of enzymes, may be useful for the identification of early invasive carcinoma. The goal of our study was to detect ST-3 expression in colorectal adenomatous polyps to see if it could be helpful for the differential diagnosis of pseudoinvasion vs. true invasion. We studied 25 polypectomy specimens which were divided histologically into 2 groups; the first consisted of 15 adenomas with invasive carcinoma, 8 of these carcinomas were more diffusely infiltrative (pT1), and 7 tended to be expansively invasive. The second group was composed of 10 adenomas with pseudoinvasion. A 35S labelled cDNA probe was used for in situ hybridization (ISH) and a monoclonal antibody (5ST-4A9) for immunohistochemistry (IHC). The distribution of ST-3 expression as detected by IHC and ISH was identical. All diffusely infiltrative carcinoma cases showed ST-3 expression, but only focally in 2 cases with marked lymphocytic infiltration. None of the expansive carcinoma or pseudoinvasion cases showed ST-3 expression. ST-3 expression seems to be an indicator of invasion, but a negative reaction for ST-3 does not rule out an expansive invasive neoplasm or a diffusely infiltrative invasive tumour with a dense lymphocytic reaction.

Clinicopathological Significance of Stromelysin-3 Expression in Colorectal Cancer

“…Porte et al [14]reported that high expression of ST3 transcripts correlated with the progression of colorectal tumors towards local invasion and liver metastasis. The protein expression of ST3, as detected by immunohistochemistry, was also related to colorectal cancers with an infiltrative pattern [17]. In the present study, higher ST3 expression was observed in tumors with an infiltrating growth pattern.…”

“…Northern blot analysis has shown that the mRNA levels of ST3 are significantly higher in colorectal carcinomas compared to non-tumorous tissue [14, 15, 16]. Furthermore, ST3 protein expression in colorectal cancer was related to an infiltrative invasion pattern and lymph vessel invasion [17, 18]. However, another study did not show significant correlations between ST3 expression and the degree of tumor invasion, metastases, or histological grade in colorectal cancer [15].…”

Stromelysin-3 expression in invasive ovarian carcinomas and tumours of low malignant potential

“…A majority of the invasive carcinomas of the breast [5,15,30], lung [2,33], skin [16,35], colon [17,31], head and neck [18,21] and pancreas [34], among others, have been found to express ST-3. The strength and extent of expression have been reported to be related to the degree [18] and pattern [17] of invasiveness.…”

“…The strength and extent of expression have been reported to be related to the degree [18] and pattern [17] of invasiveness. Recently, tissue levels of ST-3 determined using enzyme-linked immunosorbent assay (ELISA) have been found to be an independent predictor of survival in node-negative breast carcinoma [5].…”

Stromelysin‐3 is expressed by aggressive meningiomas

“…The ST3 gene initially was described as overexpressed in invasive breast carcinoma. 1 Further studies have demonstrated that ST3 is expressed in most invasive malignant epithelial tumors including those of the breast, 2-4 colon, 5,6 lung, 7,8 head and neck, 9,10 skin, 11 and urinary bladder. 12 Unlike most other proteases, ST3 expression is observed only in the cytoplasm of the fibroblasts adjacent to tumor cells, rather than in the tumor cells themselves.…”