RESUMO
HtrA proteases regulate cellular homeostasis and cell death. Their dysfunctions have been correlated with oncogenesis and response to therapeutic treatment. We investigated the relation between HtrA1-3 expression and clinicopathological, and survival data, as well as the microsatellite status of tumors. Sixty-five colorectal cancer patients were included in the study. The expression of HTRA1-3 was estimated at the mRNA and protein levels by quantitative PCR and immunoblotting. Microsatellite status was determined by high-resolution-melting PCR. We found that the HTRA1 mRNA level was higher in colorectal cancer tissue as compared to the unchanged mucosa, specifically in primary lesions of metastasizing cancer. The levels of HtrA1 and HtrA2 proteins were reduced in tumor tissue when compared to unchanged mucosa, specifically in primary lesions of metastasizing disease. Moreover, a decrease in HTRA1 and HTRA2 transcripts' levels in cancers with a high level of microsatellite instability compared to microsatellite stable ones has been observed. A low level of HtrA1 or/and HtrA2 in cancer tissue correlated with poorer patient survival. The expression of HTRA1 and HTRA2 changes during colorectal carcinogenesis and microsatellite instability may be, at least partially, associated with these changes. The alterations in the HTRA1/2 genes' expression are connected with metastatic potential of colorectal cancer and may affect patient survival.
Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Serina Peptidase 2 de Requerimento de Alta Temperatura A/genética , Instabilidade de Microssatélites , Serina Endopeptidases/genética , Adulto , Idoso , Sobrevivência Celular , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Metástase Neoplásica , Isoformas de ProteínasRESUMO
INTRODUCTION: Postoperatively diagnosed papillary or follicular thyroid cancer in subtotally thyroidectomised patients requires a completion thyroidectomy. Re-operation with a gamma probe can be particularly useful in these patients. The aim of this study was to evaluate the benefits of using an intraoperative hand-held gamma detector during completion thyroidectomy in patients with well-differentiated thyroid cancer (WTC). MATERIAL AND METHODS: 75 patients with WTC qualified for total re-thyroidectomy. In 43 patients, Group I (Nav), a hand-held gamma probe (Navigator GPS) was used intraoperatively. 32 patients were re-operated without the gamma probe (Group II). In Group I, thyroid remnants were removed based on counted gamma signals. To estimate the radicality of reoperation in both groups, thyroglobulin (Tg) levels were determined and total body scanning (TBS) - I(131) uptake - was performed. RESULTS: Total thyroidectomy with central lymphadenectomy was performed in 75 cases. The average level of Tg and iodine uptake after radicalisation was lower in Group I (Nav) than in Group II (3.32 ± 2.09 v. 4.58 ± 2.5 ng/mL, respectively, for Tg [p = 0.021] and 6.29 ± 3.38 v. 7.31 ± 2.29 ng/mL, respectively, for iodine uptake [p = 0.187]). Additionally, the frequency of postoperative complications was comparable, the difference in both groups was not significant, despite the use of the gamma probe (p = 0.109). CONCLUSIONS: The intraoperative use of a hand-held gamma detector can help to improve the radicality of a completion thyroidectomy procedure after an incomplete primary thyroid resection, but the results of this procedure in the hands of an experienced surgeon are comparable whether or not the gamma detector is used.