ABSTRACT
Extracardiac rhabdomyomas (RM) are very rare benign tumors with a poorly understood pathogenesis. In this report we describe two RM cases--a sublingual adult type tumor and a genital type tumor involving the uterine cervix. The patho-clinical characteristics, as well as the pioneer immunohistochemical analysis of ERK1/2 and AKT/mTOR pathway status is included. The expression of key proteins involved in above signaling gives new insight into the biology of extracardiac RM.
Subject(s)
Biomarkers, Tumor/analysis , Mitogen-Activated Protein Kinase 1/analysis , Mitogen-Activated Protein Kinase 3/analysis , Proto-Oncogene Proteins c-akt/analysis , Rhabdomyoma/enzymology , Signal Transduction , Sublingual Gland Neoplasms/enzymology , TOR Serine-Threonine Kinases/analysis , Uterine Cervical Neoplasms/enzymology , Aged , Biopsy , Female , Humans , Immunohistochemistry , Middle Aged , Rhabdomyoma/pathology , Rhabdomyoma/surgery , Sublingual Gland Neoplasms/pathology , Sublingual Gland Neoplasms/surgery , Treatment Outcome , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgeryABSTRACT
Tuberous sclerosis (TS) is a neurological disorder associated with the formation of tumors in several organs. Cardiac rhabdomyomas are possibly the earliest symptom of TS. Although rhabdomyomas are present in about half of TS patients, little is known of their molecular background since these tumors are rarely resected. Here we present a patient diagnosed with TS, in whom rhabdomyoma has been excised due to deterioration of hemodynamics. We found, that the tumor remained heterozygous for the affected TSC2 gene. To analyze molecular mechanisms implicated in rhabdomyoma growth, we determined the status of mTOR, Akt and Erk pathways. We found that Akt was not upregulated, while mTOR, Erk and its substrates were hyperactive. Classic activator of Erk, MEK, was only modestly active. We hypothesize that rhabdomyoma arising in TS may progress due to Erk potentiation.
