Concordance between mutations in the primary papillary thyroid carcinoma (PTC) and the paired x lymph node metastasis may elucidate the potential role of molecular targeted therapy in advanced stages. BRAF and NRAS mutations in primary PTC (n = 253) with corresponding metastatic lymph node (n = 46) were analyzed utilizing StripAssays (ViennaLab Diagnostics). Statistical analysis was performed using (SPSS, Inc.), version 24.0 with a p-value of <0.05, and concordance via kappa agreement. BRAF mutation frequency in conventional PTC (cPTC): 56.8%, papillary thyroid microcarcinoma (PTMC): 36.5%, PTMC-FV: 2.7% and PTC-FV: 4.1%. NRAS mutation frequency in PTC-FV: 28.6%, PTMC: 28.6%, PTMC-FV: 23.8%, and cPTC: 19.0%. BRAF mutation correlation with older age in cPTC (42.6 versus 33.6) years (p < 0.001) was the only significant clinicopathologic parameter. BRAF mutations were concordant in the primary and its corresponding lymph node deposits in PTC with a kappa of 0.77 (p-value < 0.0001). BRAF mutations are predominant in cPTC and PTMC while NRAS mutations in PTC-FV. BRAF mutation is conserved in metastatic lymph node deposits, thus BRAF is an early mutational pathogenetic driver. Therefore, targeted therapy is potential in recurrent and advanced stage disease.

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IntroductionTriple negative breast cancer lacks estrogen, progesterone and epidermal growth factor receptors rendering it refractory to available targetedtherapies. TNBC is associated with central fibrosis and necrosis, both indicators of tumor hypoxia. Hypoxia inducible factor 1α is up-regulated under hypoxia and its expression is associated with induction of angiogenesis resulting in proliferation, aggressive tumor phenotype and metastasis. In this study we evaluate the potential use of HIF-1α as aTNBC-specific marker.Methods62 TNBC, 64 HER2+, and 64 hormone-receptors positive breast cancer cases were evaluated for central fibrosis and necrosis, HIF-1α, HIF-1β, VEGFR3, CD31 expression and microvessel density. RNA extraction from paraffin-embedded samples, followed by quantitative real-time polymerase chain reaction (qRT-PCR) evaluation of HIF-1α and VEGF transcripts was performed on 54 cases (18 from each subtype).ResultsHIF-1α protein was expressed in 35.5% TNBC, 45.3% HER2+and 25.0% ER+/PR+ (p = 0.055; χ2 test). PCRanalysis of subgroup of breast cancers, 84.2% expressed HIF-1α protein and its transcripts, while only 66.7% expressed VEGF transcripts simultaneously with the HIF-1α protein and its transcripts. Central fibrosis and necrosis was highest in TNBC (p = 0.015; χ2 test), while MVD was comparable among all groups (p = 0.928; χ2 test). VEGFR3 was highest in TNBC expressing HIF-1α. HIF-1β protein was expressed in 32.0% of HIF-1α(+), and in (44.3%) of HIF-1α(-) breast cancer cases (p = 0.033; χ2 test). Moreover, HIF-1α expression in cases with central fibrosis and necrosis was highest in the HER2+ followed by the TNBC (p = 0.156; χ2 test).ConclusionsA proportion of TNBC express HIF-1α but not in a significantly different manner from other breast cancer subtypes. The potential of anti-HIF-1α targeted therapy is therefore not a candidate for exclusive use in TNBC, but should be considered in all breast cancers, especially in the setting of clinically aggressive or refractory disease.

Molecular genetic analysis of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations in lung adenocarcinoma has become an integral part of lung cancer diagnosis and treatment; however, their prevalence varies with ethnicity. Little is know concerning their prevalence in Arab populations. In the present study, mutational analysis for EGFR and KRAS was performed on two cohorts of the Lebanese population. Lung adenocarcinoma cases (106) underwent mutational analysis for KRAS in exon 2, codon 12 and 13 and exon 3 codon 61 by reverse hybridization using the KRAS 12/13/61 StripAssay®. Subsequently, cases with no KRAS mutations underwent EGFR mutational analysis using the EGFR RGQ polymerase chain reaction (PCR) kits for real‑time PCR on the Rotor‑Gene Q 5-plex HRM. KRAS mutations were detected in 37.7% of 106 lung adenocarcinomas; 85% had a G>T substitution in codon 12 and 13 of exon 2, and 8.5% had EGFR mutations with exon 19 deletions (88.9%) and one case with L858R substitution in exon 21. EGFR mutations were significantly correlated with females, non-smokers and well differentiation of the tumor. This is the first study in an Arab population that reports the prevalence of both EGFR and KRAS gene mutations in lung adenocarcinoma using very sensitive mutational analysis techniques. Therefore, EGFR reflex testing should be implemented in the management of lung adenocarcinomas, while KRAS testing must await the identification of effective targeted therapy.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare aggressive tumor with hepatocellular differentiation. HAS often produces alpha fetoprotein (AFP) and metastasizes to the lymph nodes and the liver. Molecular studies revealed Her2 amplification and overexpression, association with p53 mutations, but no association with KRAS mutations. EGFR and BRAF mutations have not yet been evaluated in hepatoid carcinoma of the stomach so far. Hereby, we present a case of a 41-year-old female patient with HAS with high AFP level and liver metastases. Molecular analysis revealed Her2 overexpression by immunohistochemistry (IHC), but no EGFR, KRAS, or BRAF mutations were detected. The patient underwent chemotherapy type DCX (docetaxel, cisplatinum, and capecitabine) every 3 weeks with partial response after two cycles, maintained for eight cycles, and then was on maintenance therapy with trastuzumab for 7 months before relapsing and dying 18 months from the day of diagnosis. Conclusively, HAS may be misdiagnosed as hepatocellular carcinoma; therefore, it should be considered in the differential diagnosis of multiple hepatic nodules with high AFP and no history of hepatitis, liver fibrosis or cirrhosis.

Colorectal cancer (CRC), one of the leading causes of cancer-related deaths, presents with challenging features related to its diagnosis and management. The incidence of CRC in the adolescent and young adult (AYA) population has increased over the past couple of decades despite the decline in the overall occurrence of CRC in the general population. Signet ring cell carcinoma is one of the rare histopathologic subtypes of CRC; however, it is more prevalent in AYA patients than in older adults and presents with unconventional histologic characteristics, a distinct clinical behavior, and a poor prognosis. We report a case of a primary signet ring cell adenocarcinoma of the ascending colon in a 19-year-old male who presented with unusual signs and symptoms and was diagnosed with stage IVA (T4a N0 M1, with peritoneal seeding). The unusual presentation and location of the tumor in this case warrant further investigation.

Identification of tumour biomarkers provides information on prognosis and guides the implementation of appropriate treatment in patients with many different types of cancer. In nonsmall-cell lung cancer (NSCLC), targeted treatment plans based on biomarker identification are already being utilised in the clinic. However, such predictive molecular testing is not currently a universally employed practice. This is particularly the case in developing countries where lung cancer is increasingly prevalent. In September 2012 and November 2013, a committee of 16 lung cancer experts from Africa and the Middle East met to discuss key issues related to diagnosis and biomarker testing in NSCLC and the implementation of personalised medicine in the region. The committee identified current challenges for effective diagnosis and predictive analysis in Africa and the Middle East. Moreover, strategies to encourage the implementation of biomarker testing were discussed.Ultimately, a practical approach for the effective diagnosis and predictive molecular testing of NSCLC in these regions was derived. Key issues and recommendations arising from the meetings are presented here.Abstract word count: 167 (journal limit: 250)

Lymphoepithelioma-like carcinoma (LELC) of the breast is an extremely rare tumor type. Histologically, it mimics undifferentiated nasopharyngeal carcinoma by demonstrating nests of neoplastic epithelial cells in a background of lymphoplasmacytic infiltrates. This paper reports a 62-year-old female patient with a 3 × 1.5 cm BI-RADS type IV breast mass diagnosed on excisional biopsy as LELC. The tumor is negative for estrogen and progesterone receptors and did not overexpress HER2/neu. Routine tests for clearance before surgery were performed, and patient was managed by a modified radical mastectomy with axillary lymph node dissection showing no residual tumor. Surgical CAse REports (SCARE) guidelines were followed for reporting our case. The rarity of LELC of the breast warrants the establishment and implementation of well-defined guidelines and criteria for diagnosis and management.