ABSTRACT
The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoid Tumor/genetics , Carcinoma, Large Cell/genetics , Lung Neoplasms/genetics , Small Cell Lung Carcinoma/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoid Tumor/mortality , Carcinoid Tumor/pathology , Carcinoma, Large Cell/mortality , Carcinoma, Large Cell/pathology , Comparative Genomic Hybridization , Datasets as Topic , Female , Genomics , Homeodomain Proteins/genetics , Humans , Intracellular Signaling Peptides and Proteins/genetics , Lung/pathology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Machine Learning , Male , Membrane Proteins/genetics , Middle Aged , Nerve Tissue Proteins/genetics , Prognosis , Small Cell Lung Carcinoma/mortality , Small Cell Lung Carcinoma/pathology , Survival Rate , Young AdultABSTRACT
Background The genomic grade index (GGI) completes the prognostic value of histological grade (HG). Other proliferation markers include the mitotic activity index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in node-positive breast cancer (BC) patients treated with adjuvant anthracycline-based chemotherapy in the prospective PACS01 trial. Patients and methods The five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases and analysed as continuous values. We compared the correlations of each one with the other proliferation-related parameters and with histoclinical variables including the disease-free survival (DFS). Results Expected correlations were observed between the five parameters and for each parameter with biological features (hormone-receptor and HER2 status, molecular subtypes), but the GGI displayed the strongest correlations. The GGI outperformed the prognostic performance of the four other proliferation-related parameters for the DFS in all 204 patients and in the 95 HG2 patients. In multivariate analysis including the classical prognostic factors, only GGI remained significant. Finally, the GGI outperformed the prognostic performance of MKI67 mRNA expression in a series of 1599 samples and 656 HG2 cases. Conclusions In this small pilot biomarker study ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further validation is warranted in larger series.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Ki-67 Antigen/metabolism , Mitotic Index , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/mortality , Clinical Trials, Phase III as Topic , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Neoplasm Grading , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective StudiesABSTRACT
We report the case of a fifty three years old woman who has developed in the same time a breast carcinoma and a bone chondrosarcoma. The mean of this article is to underline the strong link (statistical and phenotype) between those two cancers and to discuss the possibility of a syndrome associating breast carcinoma and bone chondrosarcoma.
