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We have developed a rapid and robust combined genetic and statistical method to establish whether multiple tumors from the same patient represent distinct primary tumors or whether they are clonally related and therefore metastatic. For the majority of case patients, histopathology reports and genetic analyses were in agreement and diagnostic confidence was improved. Importantly, in approximately one-fourth of all case patients, genetic and histopathologic analyses suggested alternative diagnoses. The results suggest that genetic analysis has implications for clinical management and can be performed rapidly as a diagnostic test with paraffin-embedded tissues.

At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.

Objective. This study assesses the role of preoperative serum CA125 levels in the planning treatment options for women diagnosed with uterine cancer. Material and Method. Ninety five consecutive patients diagnosed with uterine cancer during a four-year period were identified. Age ranged from 35 to 89 years with a mean age of 69 years. The preoperative CA125 levels were dichotomised at 28 U/mL (using ROC analysis to identify the best discriminating threshold for 5-year survival). This level was then correlated with preoperative prognostic indicators: patient age, tumour grade, and histopathological tumour cell type. Survival data was plotted using Kaplan-Meier curves and analysed using the log-rank test. Univariate and multivariate analysis were performed to identify the predictors of overall survival. Results. The mean age of patients was 69 years (range: 35–89). On univariate analysis, the use of preoperative CA125 levels of greater or less than 28 U/mL correlated significantly with age (P = 0.01), the grade of disease (P = 0.02) and unfavourable tissue type (P = 0.03). This threshold CA125 level had a sensitivity of 75%, specificity of 76%, positive predictive value of 35% and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for predicting nodal disease. Using a threshold of preoperative CA125 level of 28 U/mL (area under curve: 0.60) was also a significant predictor of 5-year survival (log-rank test, P = 0.01). Using Cox multivariate survival analysis to identify predictive preoperative factors overall, unfavourable cell type was the strongest predictor of survival (Chi square = 36.5, df = 4, and P = 0.001), followed by preoperative CA125 level (CA125 > 28 U/mL, P = 0.011) and unfavourable preoperative grade (P = 0.017). Amongst patients with a favourable histological tissue type (endometrioid), preoperative CA125 levels predicted overall survival (Chi square = 6.039, df = 2, P = 0.02); however unfavourable preoperative grade did not (P = 0.5). Overall, at five-year follow-up, while there were no deaths among the women with preoperative serum CA125 less than 12 U/mL, eleven of the twenty-three deaths (47.82%) in the study occurred in women with a preoperative CA125 more than 28 U/mL. Conclusions. A preoperative CA125 assay for women with uterine cancer is a relatively inexpensive, reproducible, and objective test which provides valuable information regarding the risk of metastatic disease and overall likelihood of long term survival. Patients with a low likelihood of metastatic/nodal disease (favourable tissue type and CA125 level < 28 U/mL) and significant comorbidities may benefit from avoiding an extended complete staging procedure. Alternatively, a high level of CA125 may prompt further imaging and multidisciplinary discussions to plan for individualised management and consideration for recruitment to clinical trials.

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