Evaluation of p27 in preinvasive and invasive malignancies of the cervix.
OBJECTIVE
p27 is a cell cycle inhibitor whose loss is commonly found in epithelial tumors. Low levels have been associated with poor prognosis. Our goal was to determine if p27 expression could be used to screen for dysplasia and if it is a prognostic factor for cervical malignancies.


METHODS
Ten normal cervices, 51 consecutive cone biopsies for preinvasive disease, and 128 consecutive hysterectomies for invasive cervical cancer (1994-1999) were stained for p27 using standard immunocytochemical techniques. All of the cervical cancer patients were managed with radical hysterectomy and lymph node dissection, except for 14 women who underwent adjuvant hysterectomy and lymph node sampling after chemoradiation.


RESULTS
There was no significant difference in p27 staining between normal cervices (all stained 4+) and preinvasive lesions (46/51 stained 4+ and 5/51 stained 3+). For the invasive lesions, 47 women had no residual disease in the hysterectomy specimen, due to prior cone biopsy (41) or radiation (6). All had 4+ p27 staining in the residual cervix. None of these women recurred. Eighty-one women had residual disease in the hysterectomy specimen; 25/81 (31%) had p27 staining of <50%. Loss of p27 was not significantly associated with invasion >50% (32 vs 27%), size >4 cm (20 vs 13%), or use of postoperative radiation (36 vs 20%). Loss of p27 was associated with lymphvascular space invasion (LVSI) (44 vs 20%, P = 0.04). Only 4 women had nodal metastasis; all 4 had p27 staining less than 50%; 6/81 (7%) women with residual disease developed recurrences and died. Of the women who died, 3/6 had p27 staining less than 50%.


CONCLUSIONS
p27 is not lost in preinvasive cervical lesions and, therefore, cannot be used to screen for dysplasia. In cervical cancers p27 staining was <50% in 31% of cases, and is associated with increased risk of LVSI. Perhaps, because of the excellent overall survival of this group of women with Stage I cervical cancer, loss of p27 staining was not associated with poor prognosis.
Goff
Barbara A
BA
Department of Obstetrics and Gynecology, University of Washington, School of Medicine, Seattle 98195, USA. bgoff@u.washington.edu
Sallin
Joshua
J
Garcia
Rochelle
R
VanBlaricom
Amy
A
Paley
Pamela J
PJ
Muntz
Howard G
HG
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27