C-Kit Protein Expression in Female Lower Genital Tract Melanoma
Carlos N Prieto-Granada, Namrata Setia, Jane L Garb, Wayne H Duke, Jean M Henneberry. Baystate Medical Center, Springfield, MA
Background: Vulvar and vaginal melanomas represent 37.1% and 7.4% of the mucosal melanomas respectively. C-Kit is a tyrosine kinase receptor altered in up to 40% of mucosal melanomas. Tyrosine kinase inhibitors (TKI) are effective in mucosal melanomas harboring specific KIT gene mutations. An association between mutated KIT and expression of C-Kit by immunohistochemistry (IHC) has been suggested. Our study explores C-Kit IHC expression in vulvovaginal melanomas and its correlation with prognostic factors.
Design: Formalin-fixed paraffin-embedded tissue blocks of vulvovaginal melanomas from 23 patients diagnosed between 1987 and 2009 were retrieved from our files. Demographic, anatomic location and prognostic data were recorded. Protein expression was semi-quantitavely scored in sections immunostained with C-Kit (DAKO 1:1000) assessing staining percentage (<20%:1+,20-50%:2+,>50%:3+) and intensity (0 to 3+) with a cumulative score ranging from 0 to 6 (0-2 negative, 3 borderline, 4-6 positive). The data was subjected to multiple regression analysis considering known melanoma prognostic factors.
Results: The age ranged from 44 to 90 years old (mean 70.8 n=23). Sixteen tumors were vulvar (70%) with 14 labial and 2 clitoral. Seven tumors (30%) were vaginal. The tumors were bulky (mean thickness of 6.12 mm.) with 17 (72%) level IV lesions (72%). Ulceration was present in 15 (65%) tumors and mitotic activity was brisk (mean mitotic count 5.4 per mm2). Lymphovascular invasion (LVI) was found in 5 (22%) cases. Scoring of IHC slides yielded 3 negative, 5 borderline and 15 positive cases (mean cumulative score 4.3). Positive/borderline cases (97% n=20) were composed of four cases staining only the melanoma in-situ component and 17 cases staining the invasive component (only in RPG:2 cases, VGP:14 cases). Multiple regression analysis revealed that C-Kit expression was significantly lower in level IV lesions compared to level II-III lesions (p=0.014) after adjusting for other significant factors. Presence of LVI further decreased C-Kit score by 2.3 (p=0.001). This data confirms that of previous studies in melanomas from other anatomical sites regarding relative loss of C-Kit expression with progression of disease.
Conclusions: We found that a great proportion (97%) of our 23 cases of female genital tract melanomas expressed C-Kit protein by IHC and that it was comparatively diminished with disease progression. In our opinion, although tempting, the association between C-Kit expression and TKI-sensitive KIT mutations in melanomas should be confirmed with genetic analysis.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 116, Wednesday Afternoon