Billie Jo Kerns

Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer

Background. Several molecular‐genetic alterations in endometrial cancers, including aneuploidy and aberrant expression of p53 and HER‐2/neu, have been associated with poor prognosis. To determine the importance of molecular‐genetic factors relative to more traditional surgical‐pathologic prognostic factors, a multivariable analysis was performed.

Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasms.

Histological grading of fibrillary astrocytic neoplasms has proved to be a valuable prognostic tool, but potentially could benefit from more objective data, such as estimates of proliferative rate. The authors have investigated the prognostic utility of quantitative Ki-67 immunoreactivity in a prospective survival analysis of 36 adult patients with astrocytoma, anaplastic astrocytoma, or glioblastoma multiforme diagnosed between 1987 and 1992. A digital image analyzer was used to assay proliferation indices (PIs) in surgical biopsy specimens obtained at first diagnosis (32 of 36) or at a second biopsy of histologically unchanged high-grade disease (4 of 36). A Ki-67 PI of > or = 7.5% was associated with higher histological grade and poorer survival, and the Ki-67 PI was more significantly related to survival (P < 0.001) than histological grade as determined by a modified Ringertz grading system (P = 0.002). Survival analysis within histological grades suggested that astrocytoma patients with PI > or = 3% may be at increased risk for shorter survival than those with PI < 3%.

Overexpression of the tyrosine phosphatase PTP1B is associated with human ovarian carcinomas

OBJECTIVE Our purpose was to determine whether protein tyrosine phosphatase 1B is overexpressed in ovarian cancers, possibly altering the balance of intracellular tyrosine phosphorylation. STUDY DESIGN The expression of protein tyrosine phosphatase 1B was assayed in frozen sections from 54 human ovarian carcinomas and seven normal ovaries by immunochemical staining with monoclonal antibody AE4-2J, which is specific for protein tyrosine phosphatase 1B. The expression of protein tyrosine phosphatase 1B-specific messenger ribonucleic acid in tumors was determined by Northern analysis. The results were analyzed statistically by means of Fishers exact test. RESULTS Minimal staining was observed in normal ovarian epithelium. In contrast, 43 of 54 (79.6%) tumors displayed increased protein tyrosine phosphatase 1B expression, which is statistically associated with malignancy. Overexpression was associated with the expression of the p185c-erbB-2, p170EGFR, and p165mCSFR growth factor receptor protein tyrosine kinases. Protein tyrosine phosphatase 1B messenger ribonucleic acid expression was inconsistently increased in tumor cells. CONCLUSION Increased expression of protein tyrosine phosphatase 1B in ovarian cancers that also express protein tyrosine kinases suggests that protein tyrosine phosphatase 1B may play a role in the growth regulation of ovarian cancers.

Acne keloidalis : transverse microscopy, immunohistochemistry, and electron microscopy

The earliest stages of acne keloidalis are not well characterized. In the present study, transverse sections of the early lesions revealed follicular units in several stages of inflammation. These follicles surrounded the central follicular units that gave rise to the clinically evident papule. Despite a spectrum of inflammatory changes, the most marked inflammation consistently occurred in the deep infundibular and isthmian levels of the hair follicles. Two follicles, presumably in the earliest stage, exhibited primarily an acute folliculitis and perifolliculitis, with destruction of the follicular wall and the release of hair. Central follicles showed predominantly acute neutrophilic or chronic lymphocytic inflammation at the upper isthmian levels and granulomatous inflammation at the deeper isthmian levels. Other follicles showed scar at the isthmian levels trapping hair fragments in the inferior portion of the follicle, with granulomatous inflammation and scarring. Sebaceous glands were absent in all stages of folliculitis in seven of eight follicular units.

Ploidy analysis of epithelial ovarian cancers using image cytometry

We used a computerized image analysis system to determine the DNA content of 103 epithelial ovarian cancers using touch imprints of frozen tumor samples. Similar to prior studies of ploidy using flow cytometry, we found that most ovarian cancers (78%) were aneuploid while a minority (22%) were diploid. There was no relationship between ploidy and stage, histologic grade, or the ability to perform optimal cytoreductive surgery. Also, like prior studies using flow cytometry, negative second-look laparotomy and survival were somewhat more common in advanced-stage patients with diploid cancers than in those with aneuploid cancers. We conclude that ploidy of ovarian cancers can be determined using a computerized image analysis system to quantitate feulgen staining of cells in touch imprints. Ploidy is unlikely to play a role in treatment planning for patients with advanced-stage disease. Larger studies of patients with early-stage disease are needed, however, to determine whether ploidy is a more accurate means of predicting which patients are most likely to benefit from adjuvant therapy.

Expression of cell regulatory proteins in ovarian borderline tumors

Tumors of borderline malignancy are still a controversial subgroup of ovarian neoplasms. The expression of several cell regulatory proteins was studied to characterize the molecular phenotype of these tumors, and to compare them with their benign and malignant counterparts.

Correlation of DNA ploidy and histologic diagnosis from prostate core-needle biopsies: Is DNA ploidy more sensitive than histology for the diagnosis of carcinoma in small specimens?

DNA ploidy has been shown to have prognostic value in adenocarcinoma of the prostate. While occasional benign lesions of the prostate may be associated with a DNA aneuploid status, most aneuploid epithelial proliferations of the prostate are carcinomas. Because of the relationship between aneuploidy and malignancy, DNA ploidy analysis might improve detection of adenocarcinoma in small core‐needle biopsy specimens. In this study, DNA ploidy analysis was performed on 186 fresh core biopsies from 32 patients who had undergone transrectal, ultrasonographically directed core‐needle biopsies. Ploidy level was determined by Feulgen staining and image analysis with a CAS 200TM image analyzer (Becton Dickinson‐Cellular Imaging Systems, San Jose, CA). The resultant DNA ploidy levels were compared with the initial histologic diagnosis and subsequent clinical and pathologic follow‐up. Nondiploid DNA patterns correlated with a diagnosis of carcinoma on core biopsy in 11 of 16 nondiploid cases and with a final diagnosis of malignancy in 13 of 16 nondiploid cases. Two patients with biopsy proven carcinoma had DNA diploid tumor patterns. Ploidy analysis had a sensitivity of 86.6% and a specificity of 73.7% in predicting the final diagnosis of malignancy. One case interpreted as DNA tetraploid by image analysis revealed seminal vesicle tissue on both the cytologic preparations and the core biopsy. Two DNA aneuploid specimen associated with cores initially read as benign or atypical demonstrated adenocarcinoma either on review of the original core biopsy or the prostatectomy specimen. The final DNA aneuploid specimen revealed acute prostatitis in the core biopsy. DNA ploidy analysis of core biopsy specimens appears to have relatively good specificity and sensitivity for the detection of prostatic carcinoma. Sampling errors appear to be the major cause of false negative results. Inappropriate measurement of seminal vesicle tissue and acute prostatitis can result in false positive results.

Intratumoral heterogeneity in primary breast carcinoma : Study of concurrent parameters

Background and Objective: Intratumoral heterogeneity for prognostic factors (ploidy, proliferation, hormone receptor positivity) has been demonstrated in primary breast carcinoma by both flow cytometric and image analysis methods. Previously, heterogeneity in tumors had been demonstrated for only singular parameters. Our objective, using maps of tumors in which discrete regions can be analyzed simultaneously for DNA index (DI) and proliferative activity, was to demonstrate heterogeneity with respect to two parameters and to determine whether any interparametric relationships existed.