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Usefulness of p16ink4a, ProEX C, and Ki-67 for the Diagnosis of Glandular Dysplasia and Adenocarcinoma of the Cervix Uteri

Negri, Giovanni M.D.; Bellisano, Giulia M.D.; Carico, Elisabetta M.D.; Faa, Gavino M.D.; Kasal, Armin B.S.; Antoniazzi, Sonia B.S.; Egarter-Vigl, Eduard M.D.; Piccin, Andrea M.D.; Palma, Paolo Dalla M.D.; Vittadello, Fabio Sc.D.

International Journal of Gynecological Pathology: July 2011 - Volume 30 - Issue 4 - p 407–413
doi: 10.1097/PGP.0b013e31820a79b0

Although the diagnostic criteria of in-situ and invasive adenocarcinomas of the cervix uteri are well established, the differentiation from benign mimics may be difficult and the morphologic features of the precursors of endocervical adenocarcinoma are still debated. In this study, we evaluated the usefulness of p16ink4a (p16), ProEX C, and Ki-67 for the diagnosis of endocervical adenocarcinoma and its precursors. Immunohistochemistry with p16, ProEX C, and Ki-67 was performed in 82 glandular lesions including 15 invasive adenocarcinomas, 29 adenocarcinomas in situ (AIS), 22 non-neoplastic samples, and 16 cases of glandular dysplasia (GD), which showed significant nuclear abnormalities but did not meet the diagnostic criteria for AIS. The immunohistochemical expression pattern was scored according to the percentage of the stained cells (0, 1+, 2+, and 3+ when 0% to 5%, 6% to 25%, 26% to 50%, and more than 50% of the cells were stained, respectively) and was evaluated for each antibody. p16 was at least focally expressed (1+ or more) in 14 of 15 invasive adenocarcinomas, in all AIS and in 7 negative samples. ProEX C and Ki-67 both scored 1+ or more in all adenocarcinomas and AIS and in 8 and 6 negative samples, respectively. Of the GD 15, 14, and 15 expressed p16, ProEX C, and Ki-67, respectively. The score differences between neoplastic and non-neoplastic samples were highly significant for each marker (P<0.001); however, the score distribution by marker differed significantly only in GD (P=0.006) in which, compared with the other markers, p16 showed more often a 3+ pattern. Our study shows that p16, Ki-67, and ProEX C may be helpful for the diagnosis of glandular lesions of the cervix uteri and may also improve the diagnostic accuracy of endocervical GD. In particularly problematic cases, the combination of p16 and a proliferation marker can provide additional help for the interpretation of these lesions.

Departments of Pathology (G.N., A.K., S.A., E.E-V.)

Hemathology (A.P.), Central Hospital Bolzano, Bolzano

Department of Cytomorphology (G.B., G.F.), Section Anatomic Pathology, University of Cagliari, Cagliari

U.O.D. Citopatologia (E.C., A.P.), IIa Facoltà Medicina e Chirurgia La Sapienza, Rome

Pathology Unit, S. Chiara Hospital of Trento (P.D.P.), Trento

Explora, Research and Statistical Analysis (F.V.), Padova, Italy

The authors declare that they have no conflict of interest.

Address correspondence and reprint requests to Giovanni Negri, MD, Department of Pathology, Central Hospital Bolzano, Via Boehler 5, 39100 Bolzano, Italy. e-mail:

©2011International Society of Gynecological Pathologists