Prognostic Factors in Early Stage Cervical Carcinomas Treated with Wertheim-Meigs Surgery

Sammanfattning: Cervical cancer is the second most common malignancy and a leading cause of morbidity and mortality among women worldwide. In Sweden, cervical cancer constitutes 2.4% of all newly diagnosed cancers and is the fifteenth cause of death.An improved estimation of the prognosis in early stages of cervical carcinomas is desirable. The most important of the established prognostic factors are tumor size, radical excision margins, and lymph node status. The objectives of this study were to assess the value of oncogene and tumor suppressor gene products, angiogenesis, proliferation markers and histopathological malignancy grading systems as predictors of pelvic lymph node metastases (LNM), tumor recurrences and death due to the disease in early stage (FIGO I-II).In a complete geographic series of cervical carcinomas treated by Wertheim-Meigs surgery, a number of clinical, biological, and histopathological prognostic factors were evaluated and long-term survival data were presented. In all, 367 woman with FIGO stage I-II cervical tumors were included.Significant prognostic factors for disease-free survival were lymph node status, radical surgical margins, and tumor size. In a multivariate Cox analysis, it was shown that lymph node status was the single most important prognostic factor (P < 0.0000001). Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage. There was also a significant (P = 0.002) association between the vascular space invasion of tumor cells and the presence of lymph node metastases.The complete malignancy grading system (MGS), partial index (PI), and invasive front grading (IFG) scores were highly significantly (P = 0.0001, P = 0.0001, P = 0.002) associated with the presence of pelvic LNM and with the disease-free survival rate. No pelvic lymph node metastases were encountered in tumors with MGS scores below 16. The predictive value (the specificity) for no pelvic lymph node metastases was 97%. The complete IFG score and the individual scores of the two variables, pattern of invasion and host response, were all significantly (P = 0 .002, P = 0.007, P = 0.0001) associated with pelvic LNM. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting LNM.The activity of the proliferation marker MIB-1 was lower in pelvic lymph node metastases than in the primary tumors. The expression ofMIB-1 in lymph nodes was a prognostic factor for disease-free survival in both univariate and multivariate analyses.In our series, it was concluded that microvessel density (CD31) and expressions of p53, bcl-2, p21 (WAF1), DNA ploidy, and S-phase fraction (FCM) did not add any further predictive or prognostic information.In conclusion, this study has confirmed that histopathological malignancy grading (MGS), the partial index (PI), and invasive front grading (IFG) in the original or modified versions can predict low and high-risk groups of tumors and therefore be of value in planning the treatment of early stage squamous cell carcinomas of the uterine cervix. The expression of the proliferative marker MIB-1 in primary tumors and in LNM seems to be a factor that should be studied further in an attempt to identify different prognostic groups of tumors requiring more individualized postoperative treatment planning.