CD10-A new prognostic stromal marker in breast carcinoma, its utility, limitations and role in breast cancer pathogenesis.

Background and Aims: Breast cancer is one of the leading causes of mortality in Indian women. Although breast cancer is an epithelial malignancy, stroma plays a key role in its development and pathogenesis. Stromal markers are now emerging as novel markers in assessing the prognosis of invasive breast cancer and have not been studied extensively till date. The aim of the present study is to study the stromal expression of CD10 in breast carcinoma, fi nd its relationship with other prognostic markers and study the role stroma plays in breast cancer pathogenesis. Materials and Methods: A total of 70 cases of breast cancer were included in the study. Representative sections were taken and hematoxylin and eosin staining was done. Immunohistochemistry was performed with ER, PR, Her2neu and CD10. Stromal expression of CD10 (>10% stromal positivity was considered positive) in invasive breast carcinoma was noted and was statistically analyzed with different known prognostic markers of breast carcinoma. Results: Stromal expression of CD10 was found to be signifi cantly associated with increasing tumor grade (P = 0.04), increasing mitotic rate (P = 0.33), worsening prognosis (P = 0.01), ER negativity (P = 0.0001), Her2neu positivity (P = 0.19) and with molecular subtypes (CD10 positivity with the HER2 type, and CD10 negativity with Luminal type). No correlation was found between CD10 overexpression and PR, age, menopausal status, tumor size, lymph node positivity and tumor stage. Conclusions: This study gives substantial proof to the various models/research papers explaining the role of stroma/CD10 in breast cancer pathogenesis. Keeping the role stroma plays in predicting prognosis and tumor response, CD10 should be included as a routine pre-chemotherapy marker in breast carcinoma. Further studies should be performed to see the role stroma plays in hormonal expression and the usefulness of CD10 to predict treatment failure in breast carcinomas receiving neoadjuvant therapy.

Scrape cytology – can it replace punch biopsy in diagnosing oral lesions.

Background: Oropharyngeal carcinoma is one of the leading causes of morbidity and mortality in Indian population due to increased use of tobacco chewing products. Mucosal biopsy is widely regarded as the gold standard for detecting oral carcinomas, but exfoliative cytology are increasingly used for early detection of malignancy and strict follow up in suspicious looking lesions. Aims & Objective: The aim of this study was to see the reliability of oral scrape cytology to detect pre-malignant and malignant oral lesions in terms of sensitivity and specificity and to see whether it can replace biopsy for diagnosing the same. Material and Methods: A total of 100 cases with oral lesions were included in the study. All patients underwent oral scrape cytology and 55 cases were followed up with punch biopsy. Sensitivity, specificity, positive and negative predictive values were calculated. Cytopathology and histopathology of premalignant and malignant lesions were compared using T test. Results: Oral cancer is most common in male (M: F 7:1). Premalignant lesions were more common in the tongue, whereas the floor of mouth was more involved by malignant lesions. Four cases were marked insufficient on cytopathology. 25% of cases were false negatives. The sensitivity, specificity, positive predictive value and negative predictive value were 91.5%, 100%, 100% and 66.7%, respectively. Statistical analysis showed P of 0.7491 suggesting that there is no significant difference between histopathology and brush cytology in assessing clinically premalignant lesions but for clinically malignant lesions P values of 0.0001 suggesting that there is significant difference between histopathology and scrape smear cytopathology in assessing malignant lesions. Conclusion: The high specificity and the high positive predictive value of oral scrape cytology makes it an ideal screening test for early detection of oral cancer. However, its low sensitivity means that it can miss cases of carcinoma, and should be followed up with biopsy with string clinical suspicion. Also, there is statistically significant difference between histopathological and cytopathological diagnosis in diagnosing dysplasia or carcinoma.

Incidence of atherosclerosis in different coronary arteries and its relation with myocardial infarction- A randomized study in 300 autopsy hearts in a tertiary care hospital.

Background: Cardiovascular disease especially myocardial infarction is one of the major causes of death in today’s world. Atherosclerosis is thought to be one of the most important factors behind the increasing incidence of myocardial infarction. Aims & Objective: This study was undertaken to find out the incidence of atherosclerosis in different coronary arteries, its correlation with increasing age and sex and with that of myocardial infarction of heart. Material and Methods: Study was performed on 300 hearts received from medicolegal autopsy cases in a tertiary care hospital, that were examined to find out the incidence of myocardial infarction and atherosclerosis in different coronary arteries. Results: Incidence of atherosclerosis and myocardial infarction was found to be more in men than in women (M:F ratio is 7:1 in atherosclerosis and 11:1 in myocardial infarction). The incidence of both increases with age. The left anterior descending artery (LAD) was the most common coronary artery involved by atherosclerosis (33%), especially type V atherosclerosis and in myocardial infarction (31%). Root of aorta was involved by atherosclerosis in only 16% cases and in 35% cases of myocardial infarction (MI). Triple vessel disease was most commonly (67.5%) associated with myocardial infarction, but a single case of myocardial infarction without involvement of any of the coronaries was reported. Regarding MI and type of atherosclerosis, more number of coronaries in MI was involved by type V atherosclerosis with occlusion, but type VI was more associated with MI. Conclusion: Atherosclerosis and myocardial infarction are more common in men and with increasing age group. Atherosclerosis of coronary arteries may lead to myocardial infarction, but the confounding effect of other lifestyle factors and age, sex and comorbid diseases can’t be excluded, for which further study is required.

Inflammation and MMPs in alcohol-induced liver diseases and protective action of antioxidants.

The consumption of alcohol causes several liver-associated diseases all over the world. Alcoholic liver diseases (ALD) include hepatic inflammation, fatty liver, hepatitis, liver cirrhosis and fibrosis and finally hepatocellular carcinoma. Although the cellular, metabolic and biochemical mechanisms for these diseases are quite explicable, the roles of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are still under investigation. The present review describes the roles and regulation of MMPs and TIMPs in different ALDs along with the involvement of other pathways. This review also summarizes the present knowledge on clinical and experimental trials with different antioxidants that help against alcohol associated liver diseases.

Curcumin delays endometriosis development by inhibiting MMP-2 activity.

Endometriosis is a common reproductive disorder believed to be associated with matrix metalloproteinases (MMPs) activities for invasion and remodeling of endometrial tissues. Ectopic endometrium has higher capacity to produce proMMP-2 than eutopic tissues; however, the role of MMP-2 during early phase of endometriosis development is still unclear. In the present study, we investigated the role of MMP-2 in establishment and development of endometriosis in mouse model. The effect of curcumin on regression of endometriosis through protease/antiprotease balance between MMP-2 and TIMP-2 was also examined. After endometrial inoculation into peritoneum, we observed a significant elevation of proMMP-2 activity from day 2 onwards. This increased MMP-2 activity was associated with decreased expression of tissue inhibitor of MMP (TIMP)-2, while a significant up-regulation of active MMP-2 activity was observed from day 3 onwards. The activation of proMMP-2 to active MMP-2 was associated with increased expression of membrane type 1 matrix metalloproteinase (MT1MMP). Curcumin at a dose of 48 mg/kg b.w. repressed the MMP-2 activity via up-regulation of bound TIMP-2 expression, thus delayed endometriosis development. In addition, curcumin inhibited production of active MMP-2 by down-regulating MT1MMP expression. Moreover, endometriotic progression was directly linked with increased MMP-2/TIMP-2 ratio which was delayed by curcumin pretreatment. In summary, our study documents the regulation of MMP-2 activity by TIMP-2 during the early phase of endometriosis development and inhibitory action of curcumin thereon.