Clinico-pathological Profile of Lung Cancer Patients in a Tertiary Care Hospital, India: A Prospective, Cross-sectional Study

Background: Adenocarcinoma (ADC) is the commonest subtype of lung cancer, though a number of studies in India have observed squamous cell carcinoma (SCC) to be the commonest histology. Majority of Indian studies on clinico-pathological profile are retrospective and there is limited data on comparison of demographic, clinical, and radiological features among histological subgroups of lung cancer. Methods: Three-hundred and twelve consecutive confirmed cases of lung cancer diagnosed from December 2014 to January 2017 were enrolled prospectively. Data pertaining to the demographic, clinical, radiological, pathological, and molecular profile were analyzed. Results: Their mean age was 57.2 � 10.8 years. Of all the lung cancer patients studied, 80.5% were males and 73.4% were smokers. Across all histological subtypes, the commonest symptom was cough (76.9%). Chest pain, hoarseness of voice, dysphagia, and neck veins engorgement were significantly higher in small cell lung carcinoma (SCLC) cases, while hemoptysis in SCC cases. The most common radiological finding was a mass lesion predominantly located, peripherally in cases with ADC and SCC lung, while centrally in SCLC. The most common site for distant metastasis was the bone (32.5%), followed by the liver, adrenal, brain, and other organs. ADC, SCC, and SCLC constituted 48.1, 32.1, and 14.4%, respectively. Incidence of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in ADC patients were 26.5% and 7.8%, respectively, with a predilection for nonsmokers. The most common EGFR mutation was exon 19 deletions. Conclusions: Adenocarcinoma lung may now be replacing SCC as the commonest type of lung cancer in Northern India. The overall incidence of EGFR mutations in ADC patients was 26.5%, with exon 19 deletion being the most common mutation

Mutational analysis of selected high-grade malignancies in a premenopausal gynecologic cancer population: a potential for targeted therapies?

Background: In 2017, there will be 107,000 cases of gynecologic cancer diagnosed in the US with an overall survival of around 70%-most occurring in post-menopausal individuals. In this study, we have examined a younger (≤ 40 years of age) subpopulation of these women with high grade/ high stage gynecologic malignancies, attempting to identify unique genetic abnormalities or combinations thereof through tissue block specimens. This information was then analyzed in light of known target therapies to see if genetic analysis in this setting would yield significant therapeutic advantage. Methods: We retrospectively evaluated patients with high grade/high stage gynecologic cancers (≤ 40 years of age), examined the presence and status of 400 oncogenes and tumors suppressor genes from Formalin-fixed, Paraffin-embedded (FFPE) tissue and functionally classified mutations by SIFT and Polyphen. Results: Twenty women were identified and stratified into positive and negative outcomes. No demographic, clinicopathologic or treatment factors were significant between these groups. Of the 400 genes evaluated, twelve mutations were significant between the groups, six with targeted therapies. Mutations associated with negative outcomes within histologies/locations were evaluated: ERBB3 in epithelial (ovarian), ALK/GPR124/KMT2D in neuroendocrine (ovarian/endometrial), ROS1/EGFR, ROS1/ERBB3/KMT2D/NIRK1 and GPR124 in sarcoma. All negative outcomes were void of mutations in APC/ABL2. A predictive model for negative outcomes in our cohort was developed from these data: AKAP9-/MBD1-/APC-/ABL2- with a mutation load of > 20.5. Conclusions: Unique multi-gene and mutational outcome correlations were identified in our cohort. Resulting complex mutational profiles in distinctly aggressive gynecologic cancers suggested potential for novel therapeutic treatment. Future larger scale studies will be needed to correlate the genotypic and phenotypic features identified here (AU)

Tumor del estroma gastrointestinal (TEGI): terapia adyuvante: ¿Cuánto tiempo? / For How Long Should Adjuvant Therapy for Gastrointestinal Stromal Tumors (GIST) Be Administered?

La cirugía es el tratamiento establecido para pacientes con tumor del estroma gastrointestinal (TEGI) primario completamente resecable. Luego de la cirugía, se pueden presentar recurrencias hasta en 50% de los casos en los 2 primeros años, especialmente en pacientes con alto riesgo. Esto justifica la terapia adyuvante con imatinib (IMB). Debido a la evidencia clínica, se sabe que 3 años de tratamiento es el tiempo establecido para pacientes con alto riesgo de recurrencia; sin embargo, también se conoce por los mismos estudios clínicos, que las recurrencias comienzan a detectarse de nuevo 6 a 9 meses después de suspender el medicamento. Se presentaron 3 pacientes llevados a cirugía con resección completa de la lesión, quienes recibieron imatinib por 3 años. Meses después de suspender el medicamento, presentaron recurrencia, lo que obligó nuevamente su administración. La duración óptima del tratamiento adyuvante con IMB no está establecida, y no es claro si el IMB realmente cura la enfermedad. Por este motivo, se plantea la necesidad de revisar por cuánto tiempo se debe administrar la terapia adyuvante con IMB y el efecto que el IMB realmente tiene sobre la enfermedad. En conclusión, por la evidencia actual se sabe que la recomendación es de 3 años de tratamiento con IMB como terapia adyuvante, pero con base en la experiencia diaria y con las recomendaciones de expertos, existen pacientes que probablemente necesiten continuar con imatinib por mucho más tiempo mientras se informan los resultados de los estudios clínicos de 5 años de tratamiento con IMB.

Surgery is the established treatment for patients with primary gastrointestinal stromal tumors (GIST) that are completely resectable. After surgery, up to 50% of patients suffer recurrences in the first two years. This is especially true for high risk patients. This is the justification for adjuvant therapy with imatinib (IMB). Based on clinical evidence, three years is the established treatment time for patients at high risk of recurrence. However, the same clinical studies also show that recurrences begin to be detectable six to nine months after discontinuation of the drug. We present the cases of three patients who underwent complete resection of GIST who then received imatinib for three years. Months after the medication was discontinued, recurrences required administration of the drug to be restarted. The optimal duration of adjuvant therapy with IMB has not been established, and it is unclear whether IMB actually cures the disease. For this reason, a review of how long adjuvant therapy with IMB should be administered and of what the effect of IMB on the disease really is was needed. In conclusion, on the basis of currently available evidence, we know that the recommendation is three years of treatment with IMB as adjuvant therapy, but, based on daily experience and expert recommendations, there are patients who probably need to continue treatment with imatinib for much longer while we wait for reports of the results of clinical studies of five year IMB treatment.

Immunohistochemical profile of high-grade ductal carcinoma in situ of the breast

OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and “not classified”. RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and “not classified” (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and “not classified” (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype. .

Quimioterapia em câncer de mama / Chemotherapy for breast cancer

Em 2010, um milhão e meio de mulheres receberão o diagnóstico de câncer de mama no mundo, sendo 49.000 no Brasil. O câncer de mama e uma área em constante evolução, exigindo, tanto da parte de mastologistas quanto dos oncologistas, rápida adaptação aos novos conceitos. Sabe-se que o câncer de mama não e uma doença única e, portanto, seu tratamento deve ser individualizado. A quimioterapia é uma parte importante do tratamento desta doença e tem evoluído recentemente, juntamente com a cirurgia, hormonioterapia, radioterapia e outros tratamentos de suporte, fazendo com que a mortalidade por esta doença continue a diminuir. Baseado em dados dos estudos de perfil molecular, e possível que mais de 50% das pacientes recebam quimioterapia adjuvante desnecessariamente. Revisa-se aqui o papel dos novos testes de perfil molecular disponíveis e o estado atual do uso de quimioterapia no câncer de mama. Nesta revisão, e dado especial enfoque ao tratamento adjuvante e neoadjuvante, sendo descritas algumas particularidades como o tratamento das pacientes idosas, da doença HER-2 positiva e da doença metastática.

In 2010, one and a half million women will be diagnosed with breast cancer worldwide, and 49, 000 in Brazil. Breast cancer is a constantly evolving area requiring from Mastologists and Oncologists a fast adaptation to new concepts. Furthermore, breast cancer does not consist of a single entity, therefore, it requires individualized treatment approaches. Chemotherapy is an important treatment modality, and it has been a rapidly evolving area that has been contributing to the decreasing breast cancer mortality observed in recent years, along with surgery, hormone therapy, radiotherapy, and other supportive treatments. Based on data from molecular profiling studies, more than 50% of the patients may be receiving unnecessary adjuvant chemotherapy. We aim to review the role of new molecular profiling tests and the current state of art in chemotherapy treatment for breast cancer. We also address the important issue of chemotherapy treatment in elderly patients, and the management of HER -2 positive and metastatic disease.

Caracterização anatomopatológica e imunofenótipica de carcinomas de mama em mulheres jovens / Pathological and molecular characterization of breast carcinomas of young women

Objetivos: Analisar características anatomopatológicas e perfil imuno-histoquímico dos carcinomas de mama em mulheres até os 35 anos. Método: Estudo retrospectivo com análise de casos recebidos no período de 1997 a 2007. Foram identificados 909 (6,6%) casos de jovens, dos quais 314 possuíam blocos de parafina disponíveis. Foi selecionado um grupo controle de 81 pacientes acima de 60 anos. Todos os casos foram revisados quanto a características anatomopatológicas. A pesquisa imuno-histoquímica de RE, RP e HER2 foi realizada em 291 casos de mulheres jovens e em 74 acima de 60 anos. Os tumores foram categorizados como luminal (RE e/ou RP positivo), HER2 (RE e RP negativos e HER2 positivo) e triplo-negativo (RE, RP e HER2 negativos). Resultados: O tipo histológico ductal invasivo foi o mais frequente nos dois grupos (95,2% em jovens e 83,90% acima de 60 anos). A frequência do tipo lobular foi menor no grupo jovem (2,5% x 12,3%), embora o subtipo pleomórfico tenha sido mais frequente. Pacientes jovens apresentaram mais frequentemente tumores de alto grau (41,7% x 28,4%) e tendência a tumores circunscritos (8,2% x 7,4%) e com necrose (23,2% x 16,0%). O perfil luminal foi mais frequente nos dois grupos, embora com proporção menor nas jovens (64,9% x 81,1%). Estas apresentaram maior frequência do perfil triplo-negativo (27,1% x 17,6%), mais superexpressão de HER2 (16,5% x 5,4%), e maior frequência do perfil HER2 puro (7,9% x 1,3%). Conclusões: Os resultados apontam para diferenças intrínsecas nos carcinomas em jovens, caracterizadas por perfis morfológico e imuno-histoquímico mais agressivos.

Aims: To analyse pathological features and immunohistochemical profile of breast carcinomas in women 35 years or less. Methods: Retrospective study with analysis of the cases received from 1997 to 2007. We identified 909 (6.6%) cases of breast cancer in young women, 314 of them with available paraffin blocks. A control group of 81 patients above age of 60 was selected. AlI the cases were revised regarding histological features. The immunohistochemical detection of ER, PR and HER2 was carried on 291 cases of young women and 74 in olders. The tumors were categorized as luminal (positive ER and/or PR), HER2 (negative ER and RP, and positive HER2), and triple-negative (negative ER, PR and HER2). Results: The ductal histological type was the most frequent one in the two groups (95.2% in young and 83.9% above 60 years). Infiltrative lobular carcinoma was less frequent in the young group (2.5% x12.3%), although the pleomorphic subtype was more frequent. Young women more often presented with high grade tumors (41.7% x 28.4%) and showed a trend to more circumscribed tumors (8.2% x 7.4%) and necrosis (23.2% x 16.0%). The luminal profile was more frequent in the two groups, although with lower frequency among younger (64.9% x 81.1%). These presented more triple-negative profile (27.1% x 17.6%), more overexpression 01 HER2 (16.5% x 5.4%), as well as the molecular profile HER2 (7.9% x 1.3%). Conclusions: The results point to intrinsic differences in the tumors arising in young women characterized by more aggressive morphological and immunohistochemical profiles.

Atrial Natriuretic Peptide System in Eyes

Atrial natriuretic peptide(ANP), a peptide hormone synthesized mainly in the cardiac atrium, has an important physiological role on the regulation of body fluid and electrolyte balance. Extraatrial ANP system has been reported. The presence of ANP in eye has also been reported. ANP in the eye has claimed to control the intraocular pressure. However, the presence of ANP and its receptors in the intraocular tissues are controversial. Therefore, the purpose of the present study was to determine the characteristics of molecular nature of ANP and its receptors in variable intraocular tissues of cow. Immunoreactive ANP was detected in aqueous humor(10+/-1 pg/ml), cornea (3.6+/-0.5 pg/mg), ciliary body(2.62+/-0.6 pg/mg), choroid(2.1+/-0.5 pg/mg), retina (1.7+/-0.2 pg/mg)and iris(1.4+/-0.5 pg/mg). Chromatographic characterization of molecular profile of ANP showed major peak corresponding to small molecular weight forms of ANP and minor peak corresponding to proANP. ANP mRNA was detected in the cornea, retina and ciliary body using reverse transcriptase-polymerase chain reaction. The production of cGMP by the activation of guanylyl cyclase was stimulated by ANP, BNP and CNP in tissue membranes of cornea, ciliary body and iris. Autoradiographic study showed that the corneal endothelium had A, B, and C subtypes of natriuretic peptide receptor. Longitudinal fibers of ciliary muscle and retina had A subtype of natriuretic receptor. These results suggest that the bovine eye has its own ANP system and ANP may have an important paracrine or autocrine function in the eye.