Diagnosis and predictive molecular analysis of non-small cell lung cancer in the Africa-Middle East region : challenges and strategies for improvement

The identification of tumor biomarkers provides information on the prognosis and guides the implementation of appropriate treatment in patients with many different cancer types. In nonesmall cell lung cancer (NSCLC), targeted treatment plans based on biomarker identification have already been used in the clinic. However, such predictive molecular testing is not currently a universally used practice. This is the case, in particular, 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 personalized 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. A practical approach for the effective diagnosis and predictive molecular testing of NSCLC in these regions was derived. We present the key issues and recommendations arising from the meetings.Pfizer Inc.http://www.journals.elsevier.com/clinical-lung-cancer/hb201

Hepatoid Adenocarcinoma of the Stomach: A Challenging Diagnostic and Therapeutic Disease through a Case Report and Review of the Literature

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

Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy.

Triple 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.62 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).HIF-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).A 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

Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer.

Despite major advances in cancer therapeutics, the prognosis for lung cancer patients is still poor and the median survival for patients presenting with advanced non-small cell lung cancer (NSCLC) is only 8-10 months. Angiogenesis is an important biological process and a relatively early event during lung cancer pathogenesis. Anti-angiogenic agents are used in treating patients with NSCLC, and their molecular biomarkers are also being assessed to predict response. A better understanding of the biology of angiogenesis in NSCLC may reveal new targets for treating this malignancy. In this article, we review the expression and prognostic impact of the angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor, in NSCLC.Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

The percentage of TNBC and Her2 + cases with positivenuclearexpression of HIF-1α that expressed HIF-1α and VEGF transcripts fold change.

<p>The percentage of TNBC and Her2 + cases with positivenuclearexpression of HIF-1α that expressed HIF-1α and VEGF transcripts fold change.</p

HIF-1αexpression in breast ductal carcinoma cells with negative (A) and weak (1+ and 2+) expression (B & C) (400x magnification).

<p>HIF-1αexpression in breast ductal carcinoma cells with negative (A) and weak (1+ and 2+) expression (B & C) (400x magnification).</p

Immunohistochemistry for HIF-1α and HIF-1β.

<p>HIF, Hypoxia inducible factor</p><p>Immunohistochemistry for HIF-1α and HIF-1β.</p

HIF-1α fold increase mRNA expression in TNBC, HER2+, ER+/PR+.

<p>HIF-1α fold increase mRNA expression in TNBC, HER2+, ER+/PR+.</p

Clinicopathologic variables of TNBC as compared to the HER2+ and ER+/PR+ breast carcinoma.

<p>* p = 0.019 indicating a significant difference at the 5% level</p><p>A,B; different letters indicate significant differences between groups</p><p>Clinicopathologic variables of TNBC as compared to the HER2+ and ER+/PR+ breast carcinoma.</p

Molecular features of TNBC as compared to the HER2⁺ and ER⁺/PR⁺ breast carcinoma.

<p>* Indicates a significant difference at the 5% level</p><p>▯Indicate significant differences between TNBC and HER2⁺ groups</p><p>^❖Indicate significant differences between TNBC, HER2⁺ and ER⁺/PR⁺ groups</p><p>Molecular features of TNBC as compared to the HER2⁺ and ER⁺/PR⁺ breast carcinoma.</p