The diagnostic significance of trophoblast cell-surface antigen-2 expression in benign and malignant thyroid lesions.

CONTEXT: Thyroid cancers are the most common malignancy of the endocrine system. Over-expression of trophoblast cell-surface antigen 2 (TROP-2) in various tumors has been found to correlate with poor prognosis and aggressive tumor behavior. AIMS: The aim of this study was to evaluateTROP-2 expression in thyroid neoplasms. SUBJECTS AND METHODS: This study contained 152 cases, including 48 follicular nodular disease (FND), 29 follicular adenoma (FA), 57 papillary thyroid carcinoma (PTC), 12 follicular thyroid carcinoma (FTC), 3 medullary thyroid carcinoma (MTC), 2 poorly differentiated thyroid carcinoma (PDTC) and 1 undifferentiated thyroid carcinoma (UDTC). TROP-2 expression was investigated via immunohistochemistry in sections prepared from paraffin blocks of the cases. RESULTS: The cases comprised 32 (21%) males and 120 (79%) females with a mean age of 46.8 years (range, 15-85 years). TROP-2 expression was observed in 74.6% of the malignant lesions of the thyroid except for medullary carcinoma, poorly differentiated and undifferentiated thyroid carcinoma. Immunoreactivity was 3.4% in FA, 41.7% of cases with FTC and 81.8% in PTC follicular variant (PTC fv). The difference between FA/FTC and FA/PTC follicular variant were both significant (P < 0.005, P < 0.001, respectively). There was no difference between FTC/PTC fv (P = 0.089). CONCLUSION: TROP-2 can be considered a useful marker for distinguishing PTC fv cases from follicular nodular disease and follicular adenoma cases because of its high sensitivity in the identification of papillary carcinomas of the thyroid.

High Mobility Group Box 1 (HMGB1) expression in gastric adenocarcinomas.

PURPOSE: High mobility group box 1 (HMGB1), the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. The purpose of this study was to investigate the expression of HMGB-1 in gastric adenocarcinoma (GC) and to evaluate its diagnostic and prognostic value. METHODS: This study included 85 cases histopathologically diagnosed with GC. Sections obtained from formalin-fixed paraffin-embedded blocks were stained immunohistochemically with HMGB1 antibody. HMGB1 expression was compared with clinicopathologic and prognostic data. RESULTS: HMGB1 expression was negative in 16 (18.8%) patients and positive in 69 (81.2%) patients. There was no correlation between HMGB1 expression and age, sex, histologic subtype of tumor, lymph node involvement (p=0.455, p=0.365, p=0.448, p=0.077, respectively ). There was a significant correlation between HMGB1 expression and tumor grade, local invasion depth (T stage) and pTNM stage (p=0.016, p=0.022, p=0.015, respectively). CONCLUSION: It was found that in the presence of HMGB1 expression, the grade of tumor differentiation decreased and the depth of invasion increased, which was associated with higher stage. These findings suggest that HMGB1 is an independent prognostic factor for GC.

Expression of human telomerase reverse transcriptase (hTERT) in thyroid neoplasms.

PURPOSE: Distinction of thyroid neoplasms that include papillary carcinoma (PC) and follicular carcinoma (FC) from benign thyroid neoplasms can be performed successfully by histopathologic examination in most of the cases. However, in some cases it may be difficult to distinct PC and FC as well as FC and follicular adenoma (FA) and also FA and the dominant nodule of multinodular goiter (MNG) histopathologically. In this study, we aimed to determine the role of expression of the human telomerase reverse transcriptase (hTERT) in the distinction of thyroid neoplasms and its relation with prognostic factors by immunohistochemical methods. METHODS: This retrospective study included 138 cases histopathologically diagnosed with benign and malignant thyroid neoplasia. Sections obtained from formalin-fixed paraffin- embedded blocks were stained with hTERT antibody. Cases were divided into hTERT-positive and -negative categories according to hTERT expression score that included percentage and intensity of staining in neoplastic cells. RESULTS: hTERT expression was negative in 93 (67.4%) and positive in 45 (32.6%) patients. Twenty-three (46.0%) of 50 PC, 12 (36.0%) of 33 FA, 1 (10.0%) of 10 FC, 4 (13.0%) of 31 MNG, 2 (66.0%) of 3 medullary carcinoma (MC) patients were found hTERT (+), showing that the difference between PC and FC was significant (p=0.034). There was also a significant difference between FA and MNG (p=0.030). There was no difference between FA and FC (p=0.117). CONCLUSION: The high expression of hTERT can be useful for making a differential diagnosis between PC and FC, and between FA and MNG when histopathological findings are equivocal.

HMGB1 expression in urothelial carcinoma of the bladder.

PURPOSE: HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in urothelial carcinoma of bladder (UCB) or not. METHODS: The study included 90 cases that were histopathologically diagnosed with UCB in the tissue samples obtained by transurethral resection (TUR). HMGB1 expression was investigated by immunohistochemistry. RESULTS: A total of 90 patients, 80 (88.9%) male and 10 (11.1%) female, were enrolled in the study. The histopathological diagnosis was infiltrating urothelial carcinoma (IUC) in 63 (70.0%) and non-invasive papillary urothelial carcinoma (NIPUC) in 27 (30.0%). When the NIPUC cases were grouped according to grade, 24 (88.9%) of the cases were low grade and 3 (11.1%) were high grade. HMGB1 expression was found positive in 51 (56.7%) and negative in 39 (43.3%) of the patients. HMGB1 expression was significantly higher in IUCs (p=0.046). CONCLUSION: The results of our study demonstrate that HMGB1 overexpression has a significant role in UCB progression and it corroborates the idea that it might be an important prognostic factor.

Expression of claudin 1, 4 and 7 in thyroid neoplasms.

The distinction of thyroid carcinoma from benign thyroid neoplasm, as well as the subtyping of papillary carcinoma (PC) and follicular carcinoma (FC), may be performed histopathologically in the majority of cases. However, in certain cases, it is difficult to histopathologically distinguish between PC and FC, as well as follicular adenoma (FA), FC and the dominant nodule of multinodular goiter (MNG-DN). The present study aimed to determine the roles of the expression levels of the tight junction proteins claudin 1, 4 and 7 in the differential diagnosis of PC, FC, FA, MNG-DN, medullary carcinoma (MC) and anaplastic carcinoma (AC). The current study included 114 cases of histopathologically diagnosed thyroid neoplasia, which were distributed as follows: 29 FA, 18 MNG-DN, 47 PC, 10 FC, 5 MC and 5 AC. The expression levels of claudin 1, 4 and 7 were examined using immunohistochemical methods. The results revealed a significant difference in claudin 1 expression between malignant and benign thyroid neoplasms (P<0.001). Claudin 1 expression was not detected in any of the MNG-DN cases, and no significant difference in claudin 1 expression levels was identified between FA and FC (P=0.653). However, a statistically significant difference was observed between FC and PC (P<0.001). Claudin 4 expression did not differ between malignant and benign thyroid neoplasms, neither between MNG-DN, FA and FC, nor between FC and PC (P=0.068, P=0.502 and P=0.481, respectively). Claudin 7 exhibited positive immunohistochemical staining in 107 patients (94%); however, no significant difference in claudin 7 expression §levels was identified between malignant and benign thyroid neoplasms among MNG-DN, FA and FC (malignant, P=0.135; benign, P=0.470). Claudin 7 exhibited positive staining in all PC and FC cases. Therefore, claudin 1 expression levels may be useful in distinguishing cases of FC and PC with overlapping histopathological features, and provide a novel immunohistochemical marker for the subtyping of thyroid carcinoma.