A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis.

Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative H&E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen κ improved from 75.8% (κ=0.52, moderate) to 84% (κ=0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (κ=0.67) to 88.7% (κ=0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an H&E review, had an impact on the decision to upgrade or downgrade cases.

Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry.

AIMS: To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. METHODS AND RESULTS: Eight pathologists from four countries (Sweden, Denmark, Norway, and Finland) received an educational lecture on the diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who: (i) determined type purely on the basis of histology; (ii) indicated whether they would apply immunohistochemistry in their routine practice; and (iii) determined type after reviewing the staining results. The results for six markers (WT1, p53, p16, HNF-1ß, ARID1A, and progesterone receptor) were determined for all 54 cases, by staining of a tissue microarray. The median concordance with central review diagnosis was 86%, and significantly improved to 90% with the incorporation of immunostaining results (P = 0.0002). The median interobserver agreement was 78%, and significantly improved to 85% with the incorporation of immunostaining results (P = 0.0002). CONCLUSIONS: Use of the immunostaining results significantly improved both diagnostic accuracy and interobserver agreement. These results indicate that ovarian carcinoma type can be reliably diagnosed by pathologists from different countries, and also demonstrate that immunohistochemistry has an important role in improving diagnostic accuracy and agreement between pathologists.

Long-term follow-up of conservatively managed incidental carcinoma of the prostate: a multivariate analysis of prognostic factors.

OBJECTIVE: To evaluate the disease-specific mortality of conservatively managed incidental carcinoma of the prostate (T1a and T1b) in relation to prognostic factors. MATERIAL AND METHODS: Since 1987 all patients with prostate cancer have been recorded and followed in the population-based Prostate Cancer Register of the South-East Healthcare Region in Sweden, which is covered by four departments of pathology. At two of these departments, tissue was obtained from 197 consecutive, previously untreated patients (aged <80 years) with incidental carcinoma who underwent transurethral resection of the prostate between 1987 and 1991. The amount of tumour, Gleason score and levels of Ki-67, p53, chromogranin A and serotonin were determined. Univariate analysis and multiple Cox regression hazard analysis were used for analysis. RESULTS: During follow-up (mean 7.8 years; maximum 17.5 years), 158 patients (80%) had died, 33 of them of prostate cancer, corresponding to 17% of the entire cohort. Of 86 patients with Gleason score < or =5, three died of prostate cancer. Independent predictors of disease-specific mortality in multivariate analysis were category T1b prostate cancer, Gleason score >5 and high immunoreactivity of Ki-67. CONCLUSIONS: Elderly men with category T1a and/or Gleason score 4-5 prostate cancer have a favourable prognosis with conservative management. Immunohistochemical staining with Ki-67 may be of help in situations where further prognostic information is required.