Identification and management of Lynch syndrome in the Middle East and North African countries: outcome of a survey in 12 countries.

BACKGROUND: Lynch syndrome (LS), the most common inherited form of colorectal cancer (CRC), is responsible for 3% of all cases of CRC. LS is caused by a mismatch repair gene defect and is characterized by a high risk for CRC, endometrial cancer and several other cancers. Identification of LS is of utmost importance because colonoscopic surveillance substantially improves a patient's prognosis. Recently, a network of physicians in Middle Eastern and North African (ME/NA) countries was established to improve the identification and management of LS families. The aim of the present survey was to evaluate current healthcare for families with LS in this region. METHODS: A questionnaire was developed that addressed the following issues: availability of clinical management guidelines for LS; attention paid to family history of cancer; availability of genetic services for identification and diagnosis of LS; and assessment of knowledge of LS surveillance. Members of the network and authors of recent papers on LS from ME/NA and neighbouring countries were invited to participate in the survey and complete the online questionnaire. RESULTS: A total of 55 individuals were invited and 19 respondents from twelve countries including Algeria, Azerbaijan, Cyprus, Egypt, Iran, Jordan, Kuwait, Lebanon, Morocco, Palestine, Tunisia, and Turkey completed the questionnaire. The results showed that family history of CRC is considered in less than half of the surveyed countries. Guidelines for the management of LS are available in three out of twelve countries. The identification and selection of families for genetic testing were based on clinical criteria (Amsterdam criteria II or Revised Bethesda criteria) in most countries, and only one country performed universal screening. In most of the surveyed countries genetic services were available in few hospitals or only in a research setting. However, surveillance of LS families was offered in the majority of countries and most frequently consisted of regular colonoscopy. CONCLUSION: The identification and management of LS in ME/NA countries are suboptimal and as a result most LS families in the region remain undetected. Future efforts should focus on increasing awareness of LS amongst both the general population and doctors, and on the improvement of the infrastructure in these countries.

Immunohistochemical Expression of Androgen Receptors (AR) in Various Breast Cancer Subtypes.

BACKGROUND: Breast carcinoma ranks the first among malignant tumours in females and is the chief cause of cancer-related mortality. Androgen in implicated in the induction of proliferation and growth of mammary cells through binding to their corresponding receptors. Androgens influence the risk of acquiring breast cancer through either direct binding to androgen receptors (AR) or indirectly through their transformation to estradiol or competing for steroid binding proteins. AIM: To study the expression of AR in various breast cancer subtypes and to elucidate its clinical significance by correlating it with clinicopathological parameters. METHODS: One hundred and fifty breast cancer cases were studied using AR immunohistochemistry, and its expression was correlated with different clinicopathologic parameters and with ER, PR, Her-2/neu and Ki 67 expression. RESULTS: AR was expressed in 91 breast carcinoma cases out of 150 examined. There was a statistically significant correlation between AR expression and tumour size, mitotic count, tumour necrosis, infiltrative borders, the hormonal status of the tumour and subsequently luminal subtypes (p < 0.05). A subset of studied TNBC (34.6%) also expressed AR. On the other hand, there was no significant correlation between AR expression and other clinicopathological parameters. CONCLUSION: Positive AR immunostaining was associated with favourable prognostic factors and luminal subtypes (A&B). Also, a subset of TNBC cases showed positive AR expression. These results introduce the current potent, next-generation AR- antagonist as possible target therapy in breast cancer. Further researches on AR expression in breast cancer are recommended on a larger scale with follow up and survival to validate the current results.

Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy. AIM: The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). MATERIAL AND METHODS: Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters. RESULTS: There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status. CONCLUSION: Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs.

Diagnostic utility of CK19 and CD56 in the differentiation of thyroid papillary carcinoma from its mimics.

BACKGROUND: Papillary Thyroid Carcinoma (PTC) is the most common type of malignant thyroid tumors. The main diagnostic clue of PTC is the presence of its characteristic nuclear features. Yet, the focal presence of these features in other thyroid lesions causes a diagnostic dilemma. AIM: To evaluate Cytokeratin 19 (CK19) and CD56 immunostains as useful diagnostic markers in distinguishing papillary thyroid carcinoma from other mimicking thyroid lesions. METHODS: Eighty cases of different thyroid lesions were submitted for immunohistochemical staining of CK19 and CD56. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were analyzed. RESULTS: CK19 was expressed in 87.8% and 21.2% of the PTC group and the non-papillary carcinoma (NPTC) group respectively, with significant difference (P<0.001). CD56 expression was lost with 81.8% of the PTC group. However, CK19 was negative in only 12.7% of the NPTC group, with significant difference (P<0.001). Comparing papillary carcinoma with papillary hyperplasia, CK19 was the most sensitive immunostain and CD56 was the most specific one, with better diagnostic accuracy in combining both immunostains. Co-expression of CK19/CD56 provided 100% sensitivity and 92% diagnostic accuracy in differentiating follicular variant of PTC from follicular adenoma. Comparing FVPTC with follicular carcinoma, sensitivity and diagnostic accuracy increased to 100% and 91.7% respectively. On distinction between papillary carcinoma (Hurthle cell variant) and Hurthle cell adenoma, sensitivity, specificity, and diagnostic accuracy were 100%, 75% and 83.3% respectively, with CK19/CD56 staining combination. Comparing papillary carcinoma on top of Hashimoto's thyroiditis with Hashimoto's thyroiditis, co-expression of both markers was associated with 100% specificity, as well as increase in PPV and diagnostic accuracy to 91%. CONCLUSION: The combined use of CK19 and CD56 is helpful in discriminating papillary thyroid carcinoma and its variants from other mimicking thyroid lesions.