Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis

Background: The development of oral cavity cancer is related to the accumulation of genetic alterations. The activation of AKT is associated with the proliferation and progression of many malignancies. It is thought that MAP kinases, together with the PI3K/AKT/mTOR signaling pathway, promote uncoordinated proliferation via inhibition of PTEN, thus increasing cell survival and mediating cancer progression. However, there are few studies regarding the expression of these proteins in oral squamous cell carcinoma (SCC). Methods: The expression of PI3K, p-mTOR, p-AKT, p-MAPK, and PTEN in 125 oral SCCs, including gingival, palate hard, and alveolar ridge tumors, was examined by immunohistochemistry and correlated with clinicopathological data and survival rates. Results: We observed PI3K, p-mTOR, p-MAPK, p-AKT, and PTEN positive staining in the cytoplasm of most SCC (92.4%, 88.2%, 88.3%, 94.2%, and 25%, respectively). Positive nuclear staining was observed for p-mTOR, PTEN, p-AKT, and p-MAPK (42.9%, 72%, 64.2%, and 58.2%, respectively). Only p-mTOR protein expression was observed on the cell membrane and was present in 44.5% of cases. A statistically significant correlation was found between p-MAPK expression and SCC clinicopathological stages III and IV (p = 0.0042). Lower rates of disease-free survival were found in patients with SCC III / IV (p = 0.001). Patients with positive nuclear staining of p-mTOR displayed a significant increase in disease-free survival rates. Discussion: The identification of prognostic and predictive markers is clinically important because oral cancer is a group of heterogeneous diseases with various biological and clinical characteristics. Conclusion: Our findings suggest that the PI3K/AKT pathway is activated in gingival, hard palate, and alveolar ridge SCCs. We have demonstrated that p-mTOR expression can function as a biomarker for survival in oral SCCs and could be a promising therapeutic target in oral SCC treatment (AU)

Synchronous thyroid and colon metastases from epidermoid carcinoma of the lung: case report / Metástases sincrônicas de carcinoma epidermoide de pulmão em tireoide e cólon: relato de caso

CONTEXT: Non-small cell lung cancer (NSCLC) progresses to distant metastases in most cases. The most frequent sites for distant metastases are the bones, central nervous system, adrenal glands and liver. Dissemination to the skin, myocardium, thyroid gland and intestine may occur, but is rare. CASE REPORT: We describe a case of squamous cell carcinoma in the lungs, with metastases in the colon and thyroid, in a 66-year-old female patient. The lesion was unresectable and chemotherapy was started. The patient evolved with intestinal subocclusion, and colonoscopy showed the presence of a polyp. Biopsy and immunohistochemical analysis on the polyp showed that it was compatible with squamous cell carcinoma of pulmonary origin. At a follow-up consultation, the patient presented a thyroid nodule. A aspiration biopsy and cellblock immunohistochemistry confirmed the squamous cell carcinoma of pulmonary origin. After third-line chemotherapy, the patient progressed with acute obstructive abdomen due to a retroperitoneal mass. She underwent exploratory laparotomy and died due to surgical complications. Metastases to the thyroid and colon are rarely reported in cases of epidermoid carcinoma of the lungs. Gastrointestinal involvement in pulmonary metastases may affect the stomach, small intestine and colon, and cases of bleeding and perforation have already been reported. Although richly vascularized, the thyroid is an infrequent site for metastases. Such sites reflect poor prognoses for the clinical evolution. We did not find any previous reports in the literature, on lung cancer with metastases concomitantly in the colon and thyroid, in a single patient.

CONTEXTO: O câncer de pulmão de células não pequenas evolui, na maioria dos casos, com metástases a distância. Ossos, sistema nervoso central, glândula adrenal e fígado são os sítios mais frequentes de metástases. Disseminação para pele, miocárdio, tireoide e intestino pode ocorrer, entretanto é rara. RELATO DE CASO: Descrevemos um caso de carcinoma espinocelular (CEC) de pulmão com metástase em cólon e tireoide, em mulher de 66 anos. A lesão era irressecável, e foi iniciada quimioterapia. A paciente evoluiu com suboclusão intestinal e a colonoscopia evidenciou pólipo colônico cuja biópsia e imunoistoquímica (IHQ) foram compatíveis com CEC de origem pulmonar. Em consulta de acompanhamento, detectou-se nódulo tireoidiano cuja punção aspirativa e IHQ de cellblock confirmaram CEC de origem pulmonar. Após quimioterapia de terceira linha, a paciente evoluiu com abdome agudo obstrutivo por massa retroperitoneal, sendo submetida a laparotomia exploradora, vindo a falecer por complicações da cirurgia. Metástases para tireoide e cólon são raramente reportadas em carcinomas epidermoides de pulmão. O envolvimento gastrointestinal por metástases de pulmão pode acometer estômago, intestino delgado e cólon, e casos de sangramento e perfuração já foram reportados. Embora ricamente vascularizada, a tireoide é sítio infrequente de metástases. Os sítios refletem prognósticos reservados na evolução clínica. Não encontramos, na literatura, relato prévio de câncer de pulmão com metástases em cólon e tireoide concomitantes em um único paciente.