p53 protein expression in synchronously occurring dedifferentiating stages of thyroid cancer in a patient with neurofibromas: A case report.

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) have been hypothesized to arise from well-differentiated thyroid carcinoma (WDTC) due to frequently reported synchronous and metachronous occurrence. Loss of normal p53 function has been implicated in this dedifferentiation process. The current case report presents a 60-year-old male with multiple neurofibromas who underwent total thyroidectomy due to multiple palpable thyroid nodules. Histopathological examination revealed three foci of predominantly papillary, but also follicular carcinoma growth pattern, and two lesions with histological features of insular and trabecular variant, with the larger one showing foci of anaplastic transition. Nuclear p53 protein accumulation, corresponding to mutant abnormally stabilized p53, was higher in more aggressive variants compared with WDTC. The somatic molecular events and downstream pathways of this dedifferentiation course have not been unraveled yet. The present case report demonstrated the simultaneous presence of three divergent histological subtypes in a single thyroid gland, with progressive enhancement of nuclear p53 protein expression, associated with mutant p53 protein, in the more aggressive variants. This is a rare case of progressive enhancement of mutant nuclear p53 protein expression in multifocal thyroid tumor areas consisting of WDTC, PDTC and ATC histological types, highlighting the possibility that WDTC can progress to PDTC and then ATC through an intricate procedure, involving loss of normal p53 function.

The role of KISS1/KISS1R system in tumor growth and invasion of differentiated thyroid cancer.

BACKGROUND/AIM: KISS1 protein and KISS1 receptor form a system that mainly promotes suppression of metastasis in various forms of cancer. We studied the relationship between KISS1/KISS1R expression and tumor progression in differentiated thyroid cancer (DTC). MATERIALS AND METHODS: Thirty-three patients diagnosed with DTC were included in the study. Immunohistochemical cytoplasmic expression was evaluated for KISS1 and cytoplasmic/membranous expression for KISS1R in thyroid cancer tissues. RESULTS: KISS1 expression was significantly higher in tumors with extrathyroidal invasion and advanced stage. KISS1R expression showed a statistically significant, moderate negative correlation with tumor size. CONCLUSION: Increased expression of KISS1 is possibly acquired to prevent further tumor invasiveness and formation of local or distant metastasis. It appears that malignant cells in DTC express increased levels of KISS1 as the tumor invades extrathyroidal tissues. Decreased expression of KISS1R seems to attenuate signaling of the KISS1/KISS1R system, possibly leading to tumor growth.

Kiss-1/GPR54 protein expression in breast cancer.

BACKGROUND: Numerous studies have shown that the Kiss-1 gene countervails the metastatic aptitude of several cancer cell lines and solid-tumor neoplasias. However, there still remains ambiguity regarding its role in breast cancer and literature has arisen asserting that Kiss-1 expression may be linked to an aggressive phenotype and malignant progression. Herein, we investigated the protein expression of Kiss-1 and its receptor GPR54 in breast cancer tissues compared to non-cancerous mammary tissues. MATERIALS AND METHODS: Paraffin-fixed cancer tissues from 43 women with resected breast adenocarcinomas and 11 specimens derived from women suffering from fibrocystic disease, serving as controls, were immunostained with Kiss-1 and GPR54 antibodies. RESULTS: Kiss-1 and GPR54 protein expression levels were significantly higher in breast cancer compared to fibrocystic tissues (p<0.05). No significant correlation was established between Kiss-1 or GRP54 expression and tumor grade, tumor size, lymph node positivity, histological type or ER status. Kiss-1 expression significantly and positively correlated with GPR54 expression in both breast cancer and fibrocystic disease specimens. CONCLUSION: Kiss-1/GPR54 expression was found to be significantly higher in breast cancer compared to non-malignant mammary tissues.