Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix

Abstract

Maspin is a serine protease inhibitor with tumor suppression activity. It is expressed in normal breast and prostate tissue but is downregulated or absent in breast and prostate tumors. Recent reports have shown that decreased expression is associated with a greater propensity for metastasis in oral squamous cell carcinomas. We know that some high-grade cervical intraepithelial neoplasia progress to invasive carcinomas while others either persist at the same degree of atypia or regress. The pattern of maspin expression in cervical intraepithelial neoplasia-grade 3, microinvasive squamous carcinomas and overtly invasive squamous cell carcinomas of the uterine cervix was studied to determine the relationship between the extent of maspin expression and the progression of cervical intraepithelial neoplasia to squamous cell carcinoma. In total, 36 cases were evaluated: 18 cases of cervical intraepithelial neoplasia-grade 3, seven cases of microinvasive squamous cell carcinoma and 11 cases of invasive squamous cell carcinoma. A monoclonal antibody was used on paraffin-embedded tissues. Immunoreactivity was scored semiquantitatively using a scale of 0-3. The sums of the scores of the different groups were compared using the Mann-Whitney U-test. A significant decrease in maspin scores was noted between cervical intraepithelial neoplasia-grade 3 vs invasive squamous cell carcinoma (Po0.005), microinvasive squamous cell carcinoma vs invasive squamous cell carcinoma (Po0.05), and cervical intraepithelial neoplasia-grade 3 vs tumor emboli (Po0.005). Although not statistically significant, scores of cervical intraepithelial neoplasia-grade 3 associated with invasive squamous cell carcinoma were lower compared to that cervical intraepithelial neoplasia-grade 3 without invasive squamous cell carcinoma. These findings suggest that maspin likely plays a role in disease progression from in situ to invasive carcinoma. Virtual absence of maspin immunopositivity in tumor emboli indicates that maspin may also play a role in metastasis. Maspin was identified as a tumor suppressor gene by subtractive hybridization from normal mammary epithelial cells. 1 It is a member of the serine protease inhibitor serpin superfamily and is located at 18q21.3, along with other serpin genes such as squamous cell carcinoma antigens 1 and 2 and PAI-2. 2 Accumulated evidence has demonstrated its role as a tumor suppressor that both inhibits cell motility and enhances the capacity for invasion and metastasis in breast cancer. [3][4][5][6][7][8] In addition, maspin expression is downregulated in prostate carcinoma cell lines and is frequently absent in primary prostate cancers. [8][9][10][11][12][13] Recent studies showed the regulation of maspin in response to androgen ablation of prostate cancer, which strongly implies that maspin plays a physiological role in growth inhibition 9 and engenders a sensitizing effect on apoptosis. 14 Oral squamous cell carcinomas that are immunopositive for maspin show a longer disease-free interval and overall survival per...

Paradoxical expression of maspin in gastric carcinomas: correlation with carcinogenesis and progression

“…Further immunohistochemical analysis indicated maspin expression was positively correlated with lymph node metastasis, in line with our results [29]. However, many articles have described a negative association between maspin expression and carcinoma progression in several malignancies, including those of the breast, prostate, colon, bladder, uterine cervix, and even stomach [8,17,[25][26][27][30][31][32]. These contradictory results might derive from specific regulation in different organs or the different genetic backgrounds of the populations studied, although definite evidence for a paradoxical mechanism remains elusive.…”

Maspin Expression in Oral Squamous Cell Carcinoma

“…30 A significant decrease of maspin between cervical intraepithelial neoplasia versus invasive squamous cell carcinoma and between microinvasive squamous cell carcinoma versus invasive squamous cell carcinoma has been reported. 7 Also, a decrease of the maspin expression in the following sequence has been described: normal breast tissue, ductal carcinoma in situ, invasive breast cancer, node metastases. 3 These facts point to a likely role of maspin in progression from in situ to invasive carcinoma.…”

“…2 These conflicting results could be attributable in part to a lack of an exact quantification of the maspin expression 23 MASPIN AND ORAL CANCER / Iezzi et al or to a variation in pathogenesis of the cancers of different organs. 7 Also, the localization of maspin positivity seems to play a relevant role in determining the patient prognosis. 2 An enhanced nuclear expression is associated with a favorable prognosis, whereas an enhanced cytoplasmic expression is associated with poor prognostic factors.…”

Immunohistochemical Features of 3,3′,4,4′-Tetrachloroazobenzene-Induced Rat Gingival Lesions

“…TOXICOLOGIC PATHOLOGY penetrating lesions in the present study demonstrated less expression of maspin. In general, loss of maspin was correlated with poor prognosis in colon, uterus, breast, prostate, skin, thyroid, and oral SCC (Amir et al 2005;Bettstetter et al 2005;Biliran and Sheng 2001;Denk et al 2007;Shams et al 2006;Xu et al 2005;Yin et al 2006;Yoshizawa et al 2009b;Xia et al 2000;Yasumatsu et al 2001). a-Smooth muscle actin and SPARC were not a prominent feature of the stroma adjacent to TCAB-induced SCC.…”