ABSTRACT
IMPORTANCE: The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is a molecular marker unique to mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland. The extent to which the transcript influences disease features and patient survival is unclear. OBJECTIVE: To determine whether the CRTC1/MAML2 fusion transcript is associated with disease stage, tumor grade, or survival outcomes in patients with MEC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical record review was performed at a tertiary-care academic medical institution. The review included 90 patients with MEC who underwent treatment from January 1, 1995, to December 31, 2011, and for whom archived formalin-fixed, paraffin-embedded tumor specimens were available. Records were reviewed for clinical, demographic, and survival data. Tumor specimens underwent fluorescence in situ hybridization. Follow-up was completed on May 15, 2014, and data were analyzed from June 1 to July 1, 2014. MAIN OUTCOMES AND MEASURES: CRTC1/MAML2 fusion transcript status. Statistical analysis determined whether transcript status was associated with disease stage, tumor grade, and/or overall and disease-free survival. RESULTS: Among the 90 eligible patients (median [range] age, 55.1 [7.8-89.2] years), 42 were female and 48 were male. Fluorescence in situ hybridization revealed a CRTC1/MAML2 translocation in 50 patients (56%). The translocations were more prevalent in intermediate-grade tumors (31 of 49 [63%]) than in high-grade (11 of 49 [22%]) and low-grade (7 of 49 [14%]) tumors; 1 tumor sample had no available grading. Similar proportions of patients with translocation-positive disease had T1 (13 of 49 [26%]), T2 (15 of 49 [31%]), T4a (14 of 49 [28%]), or T0 or Tx (8 of 49 [16%]) stages of disease. Thirty-eight of 49 patients with translocation-positive MEC (78%) had N0 stage of disease. Rates of 5-year overall survival were similar for patients with translocation-positive and translocation-negative disease (76.8% vs 75.5%, respectively; P = .17), as were rates of disease-free survival (65.2% vs 57.4%, respectively; P = .28). CONCLUSIONS AND RELEVANCE: Detection of the CRTC1/MAML2 fusion transcript provides useful information for MEC diagnosis but is not associated with differences in survival outcomes.
Subject(s)
Carcinoma, Mucoepidermoid/genetics , DNA, Neoplasm/genetics , DNA-Binding Proteins/genetics , Neoplasm Staging , Nuclear Proteins/genetics , Salivary Gland Neoplasms/genetics , Transcription Factors/genetics , Translocation, Genetic , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Mucoepidermoid/mortality , Carcinoma, Mucoepidermoid/pathology , Child , DNA-Binding Proteins/metabolism , Disease-Free Survival , Female , Follow-Up Studies , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Nuclear Proteins/metabolism , Prognosis , Retrospective Studies , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/pathology , Survival Rate , Texas/epidemiology , Trans-Activators , Transcription Factors/metabolism , Young AdultABSTRACT
Esthesioneuroblastoma is a sinonasal tumor with distinct clinicopathologic features, multiple facets, and a spectrum of behavior. Characterization of this disease is challenging, and clinically, several staging systems have been used with no consensus on a single scheme. Recently, the Hyams histological grading system has emerged as a promising prognostication tool that offers an added value to stage. This review addresses prognosis and biology in esthesioneuroblastoma. More specifically, we sought to present a critical appraisal on the value of each of these stratification systems, stage vs. grade, in identifying risk groups and guiding management.
Subject(s)
Esthesioneuroblastoma, Olfactory/pathology , Neoplasm Staging/methods , Nose Neoplasms/pathology , Esthesioneuroblastoma, Olfactory/classification , Humans , Nose Neoplasms/classification , Prognosis , Retrospective StudiesABSTRACT
PURPOSE: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC. EXPERIMENTAL DESIGN: Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias. RESULTS: Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3, and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion. CONCLUSIONS: The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC.
