Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients.

Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multiplexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics. VEGFR3 was correlated with VEGFC (p = 0.03), VEGFD (p < 0.0001), and intratumor LmVD (p = 0.03). Tumors that did not express VEGFR3 had a worse prognosis (log rank p = 0.03). VEGF was significantly correlated with survival in adenocarcinomas (log rank p = 0.014) but not in squamous cell carcinomas (log rank p = 0.5). Multivariate Cox regression analysis confirmed the independent prognostic potential of VEGFR3 (hazard ratio (HR) = 0.05; 95% confidence intervals (CI) = 0.008-0.32, p = 0.002) for all patients and VEGF (HR = 8.69, 95% CI = 1.4-53.69, p = 0.02) for adenocarcinomas. When biomarkers were multiplexed, only stage and VEGFC expression were independent predictors of survival for all patients. Weighted expression of VEGFC, VEGFR3, and stage was used to build a prognostic classifier for stage I-IIIA patients; patients in the low risk group had prolonged survival compared with high risk patients (log rank p = 0.02). There was no association between biomarkers and early recurrence or response to treatment. Angiogenic and lymphangiogenic biomarkers studied define subgroups of patients at high risk and may be useful for prognostic stratification of NSCLC patients especially those with early stage disease.

Histological expression of angiogenic factors: VEGF, PDGFRalpha, and HIF-1alpha in Hodgkin lymphoma.

Angiogenesis is a prerequisite for solid tumor growth, but there is relatively limited data regarding Hodgkin lymphoma. The purpose of this study was to examine the immunohistochemical expression of angiogenic and proliferation markers in Hodgkin biopsies in relation to clinical parameters. Immunostaining was performed on 65 Hodgkin biopsies with vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1alpha), platelet-derived growth factor receptor alpha (PDGFRalpha), Ki-67, and p53. Microvessel density (MVD) was determined by CD31 staining. In all cases, neoplastic cells and reactive background cells were evaluated. The neoplastic population expressed VEGF in 48% of the cases, HIF-1alpha in 54% of the cases, and PDGFRalpha in 95% of the cases. Both Ki-67 and p53 were positive in neoplastic cells in over 60% of the cases. The MVD had a median of 2.6/0.0625mm(2) which was not different from normal lymph nodes. VEGF in the non-neoplastic compartment showed increased staining in Ann Arbor stage I-II versus III-IV. In conclusion, VEGF, HIF-1alpha, and predominantly PDGFRalpha are expressed in neoplastic cells in the majority of Hodgkin lymphomas. As microvessel formation is not increased in Hodgkin, additional functions of these angiogenic molecules should be investigated.

Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR.

BACKGROUND: microRNA (miRNA) expression profiles are being intensively investigated for their involvement in carcinogenesis. We evaluated the prognostic value of mature microRNA-21 (miR-21) and mature microRNA-205 (miR-205) overexpression in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We studied 48 pairs of NSCLC fresh frozen tissue specimens collected at time of surgery and before chemotherapy. Highly specific amplification and quantification of mature miR-21 and mature miR-205 was achieved using looped real time RT-PCR. RESULTS: miRNA expression, determined by real time RT-PCR, was defined by DeltaDeltaCt measurements. We detected overexpression of mature miR-21 in 25 (52.0%) of the 48 NSCLC paired specimens and overexpression of miR-205 in 31 (64.6%). Overexpression was assessed after comparison of miRNA expression in NSCLC tissues and in their corresponding noncancerous tissues with respect to U6 expression. During the follow-up period, 29 of 48 (60.4%) patients relapsed, and 23 of 48 died (47.9%). Mature miR-21 was upregulated in 16 of 29 (55.2%) patients who relapsed and 15 of 23 (65.2%) patients who died. Mature miR-205 was overexpressed in 19 of 29 patients who relapsed (65.5%) and 15 of 23 patients who died (65.2%). Mature miR-21 overexpression correlated with overall survival (OS) of the patients (P = 0.027), whereas overexpression of mature miR-205 did not. CONCLUSIONS: Our results suggest that overexpression of mature miR-21 is an independent negative prognostic factor for OS in NSCLC patients.

Report of two cases of endobronchial metastases secondary to colorectal cancer.

Two cases of endoluminar/endobronchial metastases (EEM) from a secondary extrathoracic tumour are reported. The patients, eight years after the curative treatment of colorectal adenocarcinoma, were examined exhibiting pulmonary symptoms with radiological findings in the chest and endobronchial lesions as an initial presentation. The use of fiberoptic bronchoscopy of endoluminar/endobronchial lesions may help in diagnosing the origin of metastatic spread in the presence or absence of a primary tumour.

Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis C.

BACKGROUND: Recombinant interferon-alpha (IFN-alpha ) is widely used for the treatment of chronic hepatitis C. Pulmonary side effects of IFN-alpha therapy seem to be rare. So far, only a few cases of sarcoidosis in association with IFN-alpha treatment of chronic hepatitis C have been CASE REPORT: A 52-year-old woman with chronic hepatitis C developed sarcoidosis during treatment with IFN-alpha. Diagnosis of sarcoidosis was based on chest imaging studies, the increased serum angiotensin converting enzyme levels, and the histology of a biopsied cervical lymph node. Spontaneous remission was observed following IFN-alpha withdrawal. CONCLUSIONS: Use of recombinant IFN-alpha in patients with chronic hepatitis C may trigger or contribute to the development of sarcoidosis in susceptible individuals. Patients should be monitored during and following IFN-alpha therapy for the occurrence of manifestations suggesting sarcoidosis.