Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women

Krivak Bolanča, Ines and Ciglar, Srećko (2007) Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women. Collegium Antropologicum, 31 (Suppl.). pp. 107-111. ISSN 0350-6134

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Abstract

Pap smears of postmenopausal women are often misdiagnosed because of the difficulty in distinguishing atrophic epithelial cells groups only by morphological criteria. In this study we investigated the diagnostic application of immunocytochemical staining of p16INK4a on conventional Pap smear. A total of 137 cervical specimens were enrolled in this study, of which 77 and 60 cervical smears were taken from premenopausal and postmenopausal women, respectively. Two cervical smears were taken simultaneously in 68 women, one for conventional cytology and the other for immunostaining. Additional 69 cervical smears were taken from the archive, decolorized and then used for immunostaining. In premenopausal women 1 out of 14 (7.1%) with negative cytology, 7 out of 24 (29.2%) with low grade squamous intra-epithelial lesion (LSIL), all 35 (100%) with high grade squamous intraepithelial lesion (HSIL) and all 4 (100%) with squamous cell carcinoma (confirmed by histopathology) had positive staining to p16INK4a. In postmenopausal women p16INK4a positivity was observed in 4 out of 7 (57.1%) cases of LSIL, 12 out of 14 (85.7%) cases of HSIL and all 4 out of 5 (80%) different cases of carcinoma (1 cervical adenosquamous carcinoma and 3 cervical squamous cell carcinoma in situ confirmed by histopathology), but none of 34 smears with normal cytology. Twenty smears with normal cytology chosen for the negative control in this study were from the group of postmenopausal women and were as expected negative for p16INK4a immunostaining. In the group of postmenopausal women, 16 out of 60 (26.7%) cases the cytological diagnosis was established on the basis of pl6lNK4a immunostaining as being HSIL. From our preliminary study on a limited number of samples, we can however conclude that pl6INK4a immunostaining is a very useful tool for cytological diagnosis enabling to distinguish HSIL from normal, reactive or inflammatory changes.

Abstract in Croatian

Česte su pogrešne citološke dijagnoze cervikalnih razmaza žena u postmenopauzi zbog sličnosti u morfološkom izgledu stanica dubljih slojeva epitela i neoplastično promijenjenih stanica. U našoj studiji istražili smo primjenu imunocitokemijskog bojanja sa p16INK4a na cervikalnim razmazima u svrhu rješavanja tog problema. Imunocitokemijski smo obojali uzorke 77 žena u generativnoj dobi i 60 uzoraka žena u postmenopauzi. Kontrolnu skupinu su sačinjavali 20 urednih citoloških razmaza bez izraženih upalnih ili degenerativnih promjena iz skupine žena u postmenopauzi. Kod 68 pacijentica prilikom uzimanja uzoraka učinili smo 2 razmaza: jedan za citološku analizu a drugi za imunocitokemijsko bojanje. Šezdesetdevet predhodno uzetih uzoraka smo odbojali i pripremili za imunoreakciju. Kod žena generativne dobi 14 pacijentica je imalo uredan Papa-test i opažen je p16INK4a pozitivitet kod jednog uzorka (7,1%); 24 uzoraka je ocijenjeno kao SIL (skvamozna intraepitelna lezija) niskog stupnja i među njima je bilo 7 (29,2%) p16INK4a pozitivno obojenih uzoraka. Svih 39 uzoraka SIL visokog stupnja, od kojih 4 karcinoma pločastih stanica in situ naknadno histološki utvrđenih, pozitivno se obojilo. Pozitivitet p16INK4a kod razmaza starijih žena je rastao u slijedećem nizu: 0%, 57,1%, 85,7% i 80% kod 34 urednih razmaza, 4 razmaza niskog i 12 visokog SIL te 4 karcinoma naknadno histološki utvrđenih (1 adenokarcinom, 3 karcinoma pločastih stanica in situ). U skupini od 16 pacijentica, točna citološka dijagnoza SIL-a visokog stupnja postavljena je tek nakon imunocitokemijske reakcije. Na temelju našeg preliminarnog istraživanja na malom broju uzoraka, možemo zaključiti da uključivanje p16INK4a imunocitokemijskog bojanja u redovitu laboratorijsku praksu može pomoći u razlikovanju reaktivnih ili degenerativnih promjena od neoplastičnih lezija cervikalnog epitela.

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