DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b.
OBJECTIVE
To determine the utility of DNA content and DNA-related variables of proliferative activity regarding prognosis in cervical cancer.


METHODS
DNA image (ICM) andflow cytometry (FCM) were performed to determine the DNA index (DI), 5c-exceeding rate (5c-ER), S-phase fraction (SPF) and proliferation index (PI) in 163 patients with surgically staged pT1b1-pT2b squamous cell cancer of the uterine cervix and treated with primary radical hysterectomy. ICM was performed on imprint cytology, obtained from fresh tumor tissue, which was also used for FCM. Results were analyzed using the chi2 test and Cox regression analysis for risk of pelvic lymph node involvement, tumor recurrence and recurrence-free survival (RFS).


RESULTS
ICM was performed on all 163 and FCM on 133 samples. One-third of the tumors showed DNA aneuploidy. Analysis demonstrated prognostic significance of a DI > or = 1.70, with a (70:30) 2.3-fold risk of recurrence (P=.024) and reduced RFS of 10 months (P=.003) in cases of DI > or = 1.70. A high 5c-ER > 11% was associated with pelvic lymph node involvement and decreased RFS (P < or = .04). Significantly more relapses were found in tumors with SPF > 12% (70.8% vs. 29.2%, P=.007). RFS was markedly reduced in tumors with high SPF (52.3 vs. 61.1 months, P=.011). Low proliferative tumors (PI<25%) were associated with lower stage (P=.036) and increased RFS (61.2 vs. 47.1 months, P=.028). In multivariate analysis of clinicopathologic variables (pT category, nodal status, lymphovascular space involvement) and DNA related variables, pelvic lymph node involvement was the only significant predictor of RFS. In patients with nodal involvement, tumors with DI >1.70 were associated with lessfavorable outcomes.


CONCLUSIONS
DNA-related variables of cell cycle analysis were valuablefor predicting prognosis in cervical cancer patients. Tumors with DI>1.70, 5c-ER >11% and high proliferative activity (SPF>12%, PI>25%) represent a subgroup with a poor prognosis.
Horn
Lars-Christian
LC
Institute of Pathology, Leipzig University, Germany. hornl@medizin.uni-leipzig.de
Raptis
Georgios
G
Nenning
Hans
H
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D007091:Image Processing, Computer-Assisted; D008207:Lymphatic Metastasis / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011003:Ploidies; D011446:Prospective Studies; D012044:Regression Analysis; D016196:S Phase / Q000235:genetics; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery
D004273:DNA, Neoplasm