Expression of MCM-3 and MCM-7 in Primary Cutaneous T-cell Lymphomas

Primary cutaneous T-cell lymphomas is a group of rare non-Hodgkin lymphomas, originally affecting the skin. Increased proliferation activity is a hallmark of diverse tumors and the proliferation rate, measured by the expression of various markers has a predictive value regarding the malignancy course. The aim of the present study was to evaluate the prognostic value and the potential correlation between the expression of proliferation markers Ki-67, MCM-3 and MCM-7, and clinicopathological data for different types of primary cutaneous T-cell lymphomas.

Immunohistochemical reactions were performed on paraffin blocks obtained from 90 patients with mycosis fungoides (MF) and 21 patients with other CTCL (oCTCL), in comparison to 19 patients with benign inflammatory dermatosis (lichen planus, eczema), serving as control.

Statistically significant differences in the expression of Ki-67, MCM-3 and MCM-7 were observed between oCTCL vs. the control group (29% vs. 5%; 17% vs. 5%; 13% vs. 1.5%, respectively, ANOVA with Scheffé post-hoc test: p<0.01). In both, MF and oCTCL Ki-67 expression highly correlated with the expression of MCM-3 (r=0.83; p<0.001 and r=0.91; p<0.001, respectively) and MCM-7 (r=0.84; p<0.001 and r=0.87; p<0.01, respectively; Pearson correlation test). Similarly, a strong positive correlation was observed between MCM-3 and MCM-7 (r=0.81, p<0.001 and r=0.85, p<0.001). Regarding the MF group, Ki-67 and MCM-3 expression was significantly higher in advanced compared to early stages (11% vs. 3% and 15.5% vs. 5.0%, respectively, Student's t-test: p<0.05). Advanced MF had also significantly higher labeling indexes for Ki-67, MCM-3 and MCM-7 compared to benign inflammatory dermatoses (Student's t-test: p<0.01, p<0.001 and p=0.02, respectively). Considering skin involvement in MF, T1b had a significantly higher expression of Ki-67, MCM-3 and MCM-7 than T1a (p<0.001 for all comparisons) with similar observations between T2b and T2a (p=0.02; p<0.01; p=0.01, respectively, Student's t-test test). Regarding extracutaneous involvement, only MCM-3 expression in MF showed a positive relationship with both nodal and distant metastases (ANOVA with Scheffé post hoc test: p<0.01, p<0.01, respectively). Higher Ki-67 and MCM-3 expression correlated with shorter survival in MF, although the latter did not reach statistical significance (10-year survival 0.38 vs. 0.82, p=0.02, and 0.46 vs. 0.81, p=0.06, respectively; log rank test).

All studied proliferation markers may had predictive values regarding the disease severity and prognosis. Further studies are required to analyze their implementation into patient stratification and treatment process such that will improve prognosis in CTCL.