Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix

Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions relating to cellular homeostasis. Primary, HSPs are expressed in response to cellular stresses that may also include carcinogenesis. Patterns of expression have not been extensively evaluated in the multi-step carcinogenesis of cervical cancer (Normal --> HPV infection --> Cervical Precancer --> Cancer). We evaluated the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N=30), in cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV infections) (N=32), and in CIN3 (cervical precancer)(N=25) by immunohistochemistry staining (graded 0-3) and compared the results to p16INK4a, a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the lesion in a manner similar to p16INK4a (P(Trend)<0.0005). No difference in staining intensity by grade of lesion was observed for HSP90 (P(Trend)=0.8). Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were analogous to those observed for p16INK4a; HSP60 immunostaining appeared more punctate within cells than for other antigens although similar tissue patterns were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up-regulated in response to the development of CIN3 akin to p16INK4a expression.