Localization of active, dually phosphorylated extracellular signal-regulated kinase 1 and 2 in colorectal cancer with or without activating BRAF and KRAS mutations.

Colorectal cancers (CRC) often show activating mutations of the KRAS or BRAF genes, which stimulate the extracellular signal-regulated kinase (ERK) pathway, thus increasing cell proliferation and inhibiting apoptosis. However, immunohistochemical results on ERK activation in such tumors differ greatly. Recently, using a highly optimized immunohistochemical method, we obtained evidence that high levels of ERK activation in rectal adenocarcinomas were associated with resistance to radiochemotherapy. In order to determine whether KRAS and/or BRAF mutations correlate to immunohistochemically detectable increases in phosphorylation of ERK (pERK), we stained biopsies from 36 CRC patients with activating mutations in the BRAF gene (BRAFV600E: BRAF(m)), the KRAS gene (KRAS(m)) or in neither (BRAF/KRAS(n)) with this optimized method. Staining was scored in blind-coded specimens by two observers. Staining of stromal cells was used as a positive control. BRAF(m) or KRAS(m) tumors did not show higher staining scores than BRAF/KRAS(n) tumors. Although BRAFV600E staining occurred in over 90% of cancer cells in all 9 BRAF(m) tumors, 3 only showed staining for pERK in less than 10% of cancer cell nuclei. The same applied to 4 of the 14 KRAS(m) tumors. A phophorylation-insensitive antibody demonstrated that lack of pERK staining did not reflect defect expression of ERK1/2 protein. Thus, increased staining for pERK does not correlate to BRAF or KRAS mutations even with a highly optimized procedure. Further studies are required to determine whether this reflects differences in expression of counterregulatory molecules, including ERK phosphatases.

A cytologic perspective on meibomian gland carcinoma.

OBJECTIVE: To reevaluate and reestablish the reproducible diagnostic cytomorphologic features of meibomian gland carcinoma (MGCA), demonstrating the importance of fine needle aspiration cytology (FNAC) in eyelid lesions and leading to better management of the tumor. STUDY DESIGN: Cytologic smears ofpreviously diagnosed cases of MGCA over a 3-year period were collected, along with their histopathology reports. The cytomorphology of the histopathologically proven cases were reevaluated in greater detail. The cytologic smears were stained with Leishman-Giemsa cocktail and Papanicolaou stain, and the histopathologic sections were stained with hematoxylin-eosin. Special stains and immunohistochemical stains were applied as required. RESULTS: Of the 19 cases, 3 diagnosed as MGCA on cytologic examination were reported as basal cell carcinoma on histopathology. On reevaluation of the cytologic smears, in addition to the regular characteristic features of MGCA, interesting findings such as an isolated dispersed cell population in a bubbly background, signet ring cells, pseudo-mucin cell balls, giant cell reaction and hyaline-like round bodies were observed. CONCLUSION: This study emphasizes the cytomorphologic features of MGCA in addition to those described in the literature, which could be of a great help in its diagnosis. Further, it emphasizes the importance of FNAC in the diagnosis of MGCA.

Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients manuscript id: 8962091628764582.

BACKGROUND: The inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry. METHODS: In all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors. RESULTS: Eight (20%) patients of gall bladder cancer were positive for p53 expression and 10 (25%) patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age. CONCLUSION: Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results.

CA 125: a potential tumor marker for gallbladder cancer.

BACKGROUND: CA 125 is a glycoprotein and a commonly used tumor marker in ovarian carcinoma. Its use in gallbladder carcinoma (GBC) has not yet been reported. We have henceforth examined for the first time the diagnostic utility of CA 125 in patients with gallbladder diseases. PATIENTS AND METHODS: Serum CA 125 was measured in 64 patients with GBC, 47 Gallstone disease (GSD) and 23 healthy volunteers by ELISA. CA 125 level was compared between different cohorts by non-parametric test (Kruskal Wallis and Mann-Whitney test). Receiver operating characteristic curve (ROC) was constructed to see the diagnostic utility of CA 125. Its level was also correlated with age, sex and clinico-pathological parameters of the patients included in the study. RESULTS: Mean value of CA 125 in patients with GBC, GSD and healthy volunteers was 77.44 +/- 141.31 U/ml, 7.85 +/- 5.40 U/ml, and 8.08 +/- 3.26 U/ml respectively and showed a statistically significant difference (P < 0.001). CA 125 at cut off value of 11 U/ml yielded 64% sensitivity and 90% specificity in differentiating benign from malignant gallbladder disease. CA 125 level increased with stage and grade of the GBC though this was not statistically significant. A higher level of CA 125 was found in presence of gallbladder mass, weight loss, ascites and loss of appetite compared to patients with GSD. No association of CA 125 was apparent with either age or sex of the patients. CONCLUSION: CA 125 has a diagnostic potential for GBC and can differentiate GBC from GSD in light of other clinical details.