Kaplan-Meier and log-rank tests showed that MCC with lower IDO1 expression in tumor cells and with lower TDO2 and AhR expressions in TME had better overall survival than otherwise (P = .043, .008, and .035, respectively); lower TDO2 expression in TME was also associated with longer disease-specific survival (P = .016).
ALK has now been shown to play a role in the pathogenesis of several cutaneous malignancies, including secondary cutaneous systemic anaplastic large-cell lymphoma (ALCL) and primary cutaneous ALCL, melanoma, spitzoid tumors, epithelioid fibrous histiocytoma, Merkel cell carcinoma, and basal cell carcinoma.
Interphase fluorescence in situ hybridization with the anaplastic lymphoma kinase dual-color, break-apart rearrangement probe was performed on 10 randomly selected Merkel cell carcinomaanaplastic lymphoma kinase high expressors.
Furthermore, all 17 samples of MCC metastases showed ALOX15 expression with a median lymphatic vessel density (not lymph node metastases) of 5.3 (range 2.0-7.3).
The lack of the neuroendocrine master regulator ASCL1 in almost all tested MCCs points to an important role of the absence of the negative regulator REST towards the MCC neuroendocrine phenotype.
In SCLC, the related basic helix-loop-helix transcription factor HASH1 is responsible for neuroendocrine phenotype, but HASH1 transcripts were not detected in MCC cell lines.
Self-reported multiple chronic conditions (MCC) and nine instrumental activities of daily livings (IADLs) were assessed in 15 studies of the Dutch National Care for the Elderly Program (TOPICS-MDS).
Mouse survival was significantly improved for NOD-Scid-Gamma mice treated with YM155 in a dose and duration dependent manner for 3 of 4 MCV-positive MCC xenografts.
We propose that HATH1 and Brn-3c may form a transcriptional hierarchy responsible for determining neuroendocrine phenotype in Merkel cells and that lack of Brn-3c and/or HATH1 in MCC may indicate a more aggressive disease requiring closer patient follow-up.
We propose that HATH1 and Brn-3c may form a transcriptional hierarchy responsible for determining neuroendocrine phenotype in Merkel cells and that lack of Brn-3c and/or HATH1 in MCC may indicate a more aggressive disease requiring closer patient follow-up.
In summary, MCPyV-associated carcinogenesis is likely to induce the characteristic neuroendocrine features of MCC via induction of ATOH1; thus, ATOH1 can be regarded as a lineage-dependent oncogene in MCC.
This notion was confirmed in multivariate analysis suggesting that ATOH1 expression is a potential independent predictor for tumor relapse in MCC patients (P = 0.028).