Purpose: Mucinous cancers and signet ring carcinomas are distinct classes of colon cancers characterized by their production of copious quantities of intestinal goblet cell mucin, MUC2. Deletion of transcription factor HATH1ablates the biogenesis of goblet cells in developing mouse intestine, and forced expression of HATH1results in elevated expression of MUC2 in colon cancer cells. The aim of this study was to assess the possible role of HATH1 in the development of mucinous cancers and signet ring carcinomas. Experimental Design: Immunohistochemistry and confocal microscopy was used to examine HATH1 expression and subcellular distribution in normal colon and small intestine, mucinous cancers, signet ring carcinomas, and nonmucinous cancers and in precursor lesions, including hyperplastic polyps, serrated adenomas, tubular adenomas, and villous adenomas. We also analyzed the transactivation of MUC2 promoter/reporter constructs by a HATH1expression vector. Results: HATH1expression transactivated MUC2 promoter/reporter constructs, an activity that was significantly inhibited by mutation of putative HATH1-binding sites. HATH1 was expressed in the nuclei of goblet cells and in the cytoplasm and nuclei of enteroendocrine cells of the colon. In the small intestine, only cytoplasmic expression of HATH1 in enteroendocrine cells was detected. HATH1was found to be strongly expressed in the nuclei of hyperplastic polyps, serrated adenomas, villous adenomas, mucinous cancers, and signet ring carcinomas but repressed in nonmucinous cancers and tubular adenomas. Conclusions: This study confirms the importance of HATH1 for the development of intestinal secretory cells. The results further suggest that HATH1is an important factor in the up-regulation of MUC2 expression that occurs in mucinous cancers and signet ring carcinomas. In addition, the expression of HATH1 in hyperplastic polyps, serrated adenomas, and villous adenomas lends support to the hypothesis that these neoplasms are frequent precursors in mucinous cancer and signet ring carcinoma development.HATH1 and MATH1 are basic helix-loop-helix transcription factors that are the human and mouse homologues of Drosophila atonal, respectively. MATH1 was initially identified as a transcriptional activator of the developing mouse nervous system that was also expressed in nonneuronal tissues of the adult gastrointestinal tract (1). Subsequent analysis has revealed the requirement of MATH1 for the development of several cell types, including granule neurons of the cerebellum, inner ear hair cells, and secretory cells (Paneth, goblet, and enteroendocrine cells) of the intestinal epithelium (2 -6). Thus, MATH1 plays critical roles in regulating transcription and differentiation in diverse cell types.Colorectal cancers are derived from the cells of the colonic epithelium. They develop as one of several distinct histologic subtypes. A major distinguishing characteristic of colon cancers is the degree to which they produce and secrete goblet cell mucin, MUC2. The majority of...

PurposeThe increasing incidence of thyroid cancer worldwide has drawn attention to the needs for assessing and managing health-related quality of life (HRQoL) of thyroid cancer survivors. We conducted this study to validate the Korean version of the thyroid cancer-specific quality of life (THYCA-QoL) questionnaire.MethodsData obtained from 227 thyroid cancer survivors were analyzed using standard validity and reliability analysis techniques. Reliability was assessed by measuring internal consistency via Cronbach α coefficient, and validity was assessed by determining the Pearson correlation coefficient between the THYCA-QoL questionnaire and the following relevant assessment tools: the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30), the Korean version of Brief Fatigue Inventory (BFI-K), the Korean version of Brief Encounter Psychosocial Instrument (BEPSI-K), Goldberg Short Screening Scale for Anxiety and Depression, and a nine-item Patient Health Questionnaire (PHQ-9). A multitrait scaling analysis was performed to assess each item's convergent and discriminant validity.ResultsThe reliability of the THYCA-QoL questionnaire was confirmed by Cronbach α coefficients for multiple-item scales which ranged from 0.54 (sensory) to 0.82 (psychological). Except for a single item (sexual interest), the questionnaire's validity was established by significant correlation observed between scales in the THYCA-QoL questionnaire and scales used in other assessment tools. A multitrait scaling analysis confirmed that all scales met the recommended psychometric standards.ConclusionThe Korean version of the THYCA-QoL questionnaire is a reliable and valid assessment tool that can be used in combination with the EORTC QLQ-C30 to assess the HRQoL of thyroid cancer survivors in Korea.