ABSTRACT
Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5 to 8.7% of CRCs. It has been shown that SAC has a poorer prognosis and has different molecular and immunohistochemical features compared with conventional carcinoma (CC) but, to date, only one previous study has analyzed its mRNA expression profile by microarray. Using a different microarray platform, we have studied the molecular signature of 11 SACs and compared it with that of 15 matched CC with the aim of discerning the functions which characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a validation set of 70 SACs and 70 CCs to assess their diagnostic and prognostic values. Microarray data showed a higher representation of morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related functions and also an overexpression of fascin1 (actin-bundling protein associated with invasion) and the antiapoptotic gene hippocalcin in SAC all of which were validated both by quantitative real-time PCR (qPCR) and immunohistochemistry. Fascin1 expression was statistically associated with KRAS mutation with 88.6% sensitivity and 85.7% specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity = 100%). Evaluation of these markers in CRCs showing histological and molecular characteristics of high-level microsatellite instability (MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular profiling demonstrates that SAC shows activation of distinct signaling pathways and that immunohistochemical fascin1 and hippocalcin expression can be reliably used for its differentiation from other CRC subtypes.
Subject(s)
Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Transcriptome , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carrier Proteins/genetics , Carrier Proteins/metabolism , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , DNA Mutational Analysis , Female , Gene Expression , Hippocalcin/genetics , Hippocalcin/metabolism , Humans , Male , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Microsatellite Instability , Middle Aged , Multivariate Analysis , Neuronal Apoptosis-Inhibitory Protein/genetics , Neuronal Apoptosis-Inhibitory Protein/metabolism , Oligonucleotide Array Sequence Analysis , OncogenesABSTRACT
El hidradenoma nodular maligno o hidradenocarcinoma es un tumor maligno de glándula sudorípara, extremadamente infrecuente, que generalmente surge de novo aunque se han descrito unos pocos casos surgidos sobre un hidradenoma nodular. El comportamiento biológico de este tipo de neoplasias es altamente agresivo con recurrencias locales y metástasis ganglionares en un alto porcentaje.El tratamiento de elección de estos tumores es la escisión quirúrgica con márgenes amplios si bien en la enfermedad metastásica estaría indicado el tratamiento neoadyuvante con quimio y/o radioterapia. Recientemente, se ha propuesto el tratamiento con trastuzumab para los casos con sobreexpresión de Her-2/neu así como la realización de ganglio centinela.Presentamos el caso de un hidradenocarcinoma surgido en un hidradenoma nodular en piel de región intermamaria en una mujer de 55 años. El tumor fue tratado con escisión amplia y se realizó ganglio centinela. La paciente recibió radioterapia posquirúrgica sin que haya evidencia de metástasis tras un año de seguimiento(AU)
Malignant nodular hidradenoma or hidradenocarcinoma is a rare, malignant tumour of sweat glands that usually arises de novo, although a few cases originating in a nodular hidradenoma have been reported. They are very aggressive neoplasms that recur locally and frequently metastasize to the lymph nodes. The treatment of choice is surgical excision with wide margins, followed by chemotherapy and/or radiotherapy when metastases have occurred. Recently, sentinel lymph node sampling and treatment with Trastuzumab have been proposed for cases with overexpression of Her-2/neu. A case of hidradenocarcinoma arising in a nodular hidradenoma of the breast skin of a 55 year old woman is presented. The tumour was surgically removed with a wide excision and the patient treated with postoperative radiotherapy. She is alive and well without evidence of metastatic disease one year later(AU)
