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Background and Objectives: The monoclonal antibody MIB-1 is an immunohistochemical marker reacting most strongly with cells in late S phase, G2, and M portions of the cell cycle. This antibody, reactive in formalin-fixed, paraffin-embedded tissue, allows the quantitation of a proliferation index (PI) in both current clinical cases and archival material using a computerized image analyzer (CIA)., Methods: Since many laboratories make use of automated immunohistochemistry (AIH), this study was performed to explore the technical feasibility of using AIH (Ventana ES 320) in combination with CIA (CAS 200) to evaluate MIB-1 PI as a prognostic marker as assessed by overall survival in 50 archival (formalin-fixed, paraffin-embedded), advanced stage primary ovarian carcinomas., Results: Exploratory methods confirmed that 15% was a cutpoint that could dichotomize these 50 patients into two prognostic groups based on overall survival. The median survival of patients whose carcinoma had a high MIB-1 expression (> or = 15%) was 16 months compared with 30 months in the patients whose tumors demonstrated low MIB-1 expression (< 15%, P = 0.01). After adjustment for age, MIB-1 retained its prognostic significance (P = 0.02). Patients 60 years and older had shorter survival than younger patients (P = 0.06), but these two groups did not differ with respect to PI (P = 0.76). Those patients with a negative second look laparotomy had a longer median survival of 70 months compared with 18.5 months in patients with a positive second look (P < 0.001); the median PIs were 17% and 27%, respectively (P = 0.36). There were no significant relationships between clinical stage, nuclear grade, DNA ploidy, p53, and either survival or PI., Conclusions: In this study, we concluded that the combination of AIH and CIA yielded a reliable quantitation of MIB-1 proliferative index and that this proliferative marker had prognostic significance in late stage ovarian carcinoma. Further studies in a larger group of patients are needed to confirm the relationship between proliferation index and other known clinicopathologic and genetic variables.

The quantitation of estrogen and progesterone receptors (ER and PgR) has become the standard of care in the evaluation of patients with primary breast carcinoma. It has been demonstrated that ER and PgR detected by immunohistochemical methods in formalin-fixed paraffin-embedded tissue can be quantified by computerized image analysis. In this study, ER and PgR levels were determined by using an automated immunochemistry stainer (Ventana ES 320) and an image analyzer (CAS 200) in a series of 236 patients with stage I/II carcinoma of the breast. The degree of correlation of the ER and PgR levels determined by the dextran-coated charcoal method (DCC) with image analysis quantitation was high (r=0.75). The agreement between both methods was 77% for ER and 73% for PgR. Hormone receptor levels were correlated with prognosis as determined by overall survival. An ER level of 30 fmol/mg as determined by image analysis was established to stratify the patient population most effectively into favorable and unfavorable prognostic groups (P=0.003). An ER level of 20 fmol/mg for prognostic stratification reached statistical significance (P=0.03). The DCC method was not able to stratify the patients into prognostic groups at the traditionally accepted cutpoint of 10 fmol/mg (P=0.52). We conclude that when used in combination, automated immunohistochemistry and quantitative image analysis offer a favorable alternative to the DCC method in assessment of ER and PgR status in human mammary carcinoma. In addition, quantitative immunocytochemistry techniques may prove superior to the DCC method in specimens in which there is limited tumor volume (including fine-needle aspirates), stroma-rich tumors, and early-stage lesions including intraductal carcinoma.