R. Gordon Wright

Prognostic significance of muc1 epithelial mucin expression in breast cancer

The epithelial mucin produced by the MUC1 gene is present in the apical cell membrane of normal breast epithelial cells and is highly expressed in many breast cancers. Several studies have provided conflicting evidence regarding the relationship between MUC1 expression and survival in breast cancer patients. In this study a detailed immunohistological analysis of MUC1 expression was performed using monoclonal antibody BC2 and was related to other tumor characteristics and patient survival. Patients whose tumors showed MUC1 expression in greater than 75% of tumor cells had significantly poorer disease-free and overall survival (P < .05). The proportion of cells showing cytoplasmic MUC1 expression was prognostically significant, but the proportion of cells that lined gland spaces showing apical membrane staining was of no prognostic significance. A high level of MUC1 expression was significantly associated with the presence of axillary node metastases and estrogen receptors but not with other tumor characteristics.

Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A in ovarian cancer is associated with progression and unfavourable prognosis

Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin‐dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas only 11% of malignant cancers were p16 negative. A high proportion of p16‐positive tumour cells was associated with advanced stage and grade, and with poor prognosis in cancer patients. For FIGO stage 1 tumours, a high proportion of p16‐positive tumour cells was associated with poorer survival, suggesting that accumulation of p16 is an early event of ovarian tumorigenesis. In contrast to tumour cells, high expression of p16 in the surrounding stromal cells was not associated with the stage and grade, but was associated with longer survival. When all parameters were combined in multivariate analysis, high p16 expression in stromal cells was not an independent predictor for survival, indicating that low p16 expression in stromal cells is associated with other markers of tumour progression. High expression of p16 survival in the stromal cells of tumours from long‐term survivors suggests that tumour growth is limited to some extent by factors associated with p16 expression in the matrix. Int. J. Cancer 74:57–63.

Performance measures for Australian laboratories reporting cervical cytology: a decade of data 1998–2008

Aim: Performance measures for Australian laboratories reporting cervical cytology are a set of quantifiable measures relating to the profile and accuracy of reporting. This study reviews aggregate data collected over the ten years in which participation in the performance measures has been mandatory. Methods: Laboratories submit annual data on performance measures relating to the profile of reporting, including reporting rates for technically unsatisfactory specimens, high grade or possible high grade abnormalities and abnormal reports. Cytology‐histology correlation data and review findings of negative smears reported from women with histological high grade disease are also collected. Suggested acceptable standards are set for each measure. This study reviews the aggregate data submitted by all laboratories for the years 1998–2008 and examines trends in reporting and the performance of laboratories against the suggested standards. Results: The performance of Australian laboratories has shown continued improvement over the study period. There has been a fall in the proportion of laboratories with data outside the acceptable standard range in all performance measures. Laboratories are reporting a greater proportion of specimens as definite or possible high grade abnormality. This is partly attributable to an increase in the proportion of abnormal results classified as high grade or possible high grade abnormality. Despite this, the positive predictive value for high grade and possible high grade abnormalities has continued to rise. Conclusion: Performance measures for cervical cytology have provided a valuable addition to external quality assurance procedures in Australia. They have documented continued improvements in the aggregate performance, as well as providing benchmarking data and goals for acceptable performance for individual laboratories.

External quality assurance in nongynecologic cytology: The Australasian experience: EQA in Nongynecologic Cytology

The Royal College of Pathologists of Australasia Cytopathology Quality Assurance Program has operated an external quality assurance program in nongynecologic cytopathology since 1993. Glass slide preparations of a wide range of nongynecologic cases were circulated to approximately 200 cytopathology laboratories in 16 countries.

The kiribati immunohistochemistry problem

Aim The Gold Coast Hospital receives surgical specimens from The Republic of Kiribati for processing and reporting. The specimens have prolonged fixation with formalin of unknown concentration. Conventional histopathology slides were generally inter-pretable whereas immunohistochemical staining produced widely discrepant results. In this investigation the factors affecting immu-nohistochemical staining across a range of commonly used diagnostic antibodies (vimentin, cytokeratin 7, CD34 and 45, NSE) were studied. Methods Fixation time, fixative pH and specific gravity, an indirect method of formalin concentration measurement, were performed on twenty Kiribati specimens. Immunohistochemistry was performed using optimal antigen retrieval methods and stains scored with a standard reporting system. Results The formalin in all of the 20 specimen containers was highly concentrated and markedly acidic. Staining intensity was generally weak, patchy and unreliable in all specimens across all five antibodies. Low fixative pH appeared to adversely affect staining intensity. No direct relationship with fixation time was found. Discussion Inadequately diluted and poorly buffered formalin produced unreliable immunohistochemical results. Education of Kiribati laboratory and theatre staff would improve fixation and immunohistochemistry results. The measurement of formalin concentration and pH will allow the histopathology laboratory to determine whether immunohistochemistry is appropriate for a particular specimen.