The Pattern of Expression of Human Placental Lactogen Across Normal, Lactational, and Malignant Mammary Epithelium.

The immunoexpression of human placental lactogen (hPL) in mammary epithelium is not well studied in the literature. Our overall objective was to delineate the distribution pattern of hPL across mammary epithelia of varying levels of differentiation. This is the first research to study the level of expression of hPL in human lactational change epithelium. Immunohistochemistry (IHC) for hPL was performed on archival formalin-fixed paraffin-embedded tissue blocks of 97 cases. These consisted of 53 invasive ductal carcinomas, 21 lactational change cases, and 23 cases of normal mammary tissue. The results of this study show underexpression of hPL in malignant epithelium compared to normal and lactational groups individually and combined as a non-malignant group. However, a higher expression of hPL was noted in mammary carcinoma of axillary lymph node (ALN)-positive patients compared to ALN-negative cases. There was no statistically significant difference between hPL expression and tumor grade, estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptor 2 (HER2) status. The comparison of the immunoexpression of hPL in malignant epithelium versus lactational change epithelium may provide the basis for future studies on the possible role of hPL in the protective mechanism of lactation tissue from carcinogenesis. Our results could be explained by the proposed mechanism in the literature, which is that breast cancer cells have a potential inhibitory effect on the translation of human chorionic somatotropin hormone (CSH) mRNA into hPL protein. Our results support the literature findings of a poorer prognostic outcome for breast malignancies when hPL is expressed but require further studies using a more comprehensive range of clinical parameters.

The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis.

The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs) are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs) in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC) for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal) carcinoma, particularly HER-2-negative cancers.

The pattern of expression and role of triiodothyronine (T3) receptors and type I 5'-deiodinase in breast carcinomas, benign breast diseases, lactational change, and normal breast epithelium.

AIM: : To study the pattern of expression of triiodothyronine (T3) receptors and type I 5'-deiodinase in various breast pathologies comparing malignant and nonmalignant epithelia that include lactational change. METHODS AND RESULTS: A retrospective study was performed on formalin-fixed, paraffin-embedded archival material from 146 cases of carcinomas, normal breast tissue, breast tissue showing lactational change, and benign breast lesions. Archive tissue blocks were selected and sections were cut for immunohistochemistry to study the expression of thyroid hormone receptor α-1 (THR-α1) in the cytoplasm and nuclei of cells in tissues under study. Thick sections were cut for type I 5'-deiodinase evaluation using reverse transcriptional PCR.THR-α1 showed no nuclear expression in the carcinoma group. Combined nuclear and cytoplasmic expression was seen in 47.6%, 63.4%, 64.3%, and 58.3% in the benign, fibrocystic, fibroadenoma, and lactational change groups, respectively, compared with only 17.4% of cases in the carcinoma group. This suggests deregulation of the thyroid hormone in breast cancer. Theories for the possible role of thyroid hormone in the pathogenesis of breast cancer are discussed.Type I 5'-deiodinase was not shown to be differentially expressed in malignant versus nonmalignant groups. CONCLUSIONS: Our study revealed substantial reduction in the protein expression profile of THRs in malignant versus nonmalignant mammary epithelium suggesting a possible role in breast cancer development. The presence of THRs in mammary epithelium seems to be protective against the development of breast cancer. This could serve as a potential prognostic and therapeutic target for breast cancer.

Development and validation of a tool to evaluate the quality of medical education websites in pathology.

BACKGROUND: The exponential use of the internet as a learning resource coupled with varied quality of many websites, lead to a need to identify suitable websites for teaching purposes. AIM: The aim of this study is to develop and to validate a tool, which evaluates the quality of undergraduate medical educational websites; and apply it to the field of pathology. METHODS: A tool was devised through several steps of item generation, reduction, weightage, pilot testing, post-pilot modification of the tool and validating the tool. Tool validation included measurement of inter-observer reliability; and generation of criterion related, construct related and content related validity. The validated tool was subsequently tested by applying it to a population of pathology websites. RESULTS AND DISCUSSION: Reliability testing showed a high internal consistency reliability (Cronbach's alpha = 0.92), high inter-observer reliability (Pearson's correlation r = 0.88), intraclass correlation coefficient = 0.85 and κ =0.75. It showed high criterion related, construct related and content related validity. The tool showed moderately high concordance with the gold standard (κ =0.61); 92.2% sensitivity, 67.8% specificity, 75.6% positive predictive value and 88.9% negative predictive value. The validated tool was applied to 278 websites; 29.9% were rated as recommended, 41.0% as recommended with caution and 29.1% as not recommended. CONCLUSION: A systematic tool was devised to evaluate the quality of websites for medical educational purposes. The tool was shown to yield reliable and valid inferences through its application to pathology websites.