Diagnostic Utility of Thyroid Transcription Factor-1 in Ovarian Carcinoma and Its Relationship With Clinicopathologic Prognostic Parameters.

Although thyroid transcription factor-1 (TTF-1) is considered a relatively sensitive and specific marker for lung and thyroid neoplasms, it can occasionally be expressed in other tumors. Few immunohistochemical studies have been conducted on TTF-1 expression in ovarian carcinomas with discrepant results. To date, only 1 study compared different TTF-1 clones in ovarian carcinoma. This study is designed to evaluate the expression of TTF-1 clones in ovarian carcinomas and investigate TTF-1 association with clinicopathologic prognostic parameters. A retrospective immunohistochemical study was conducted on 62 primary ovarian carcinomas and 15 normal ovarian tissues using 2 clones of TTF-1 antibody (SPT24 and 8G7G3/1). Nuclear expression of SPT24 and 8G7G3/1 clones of TTF-1 was detected in 17.7% and 3.2% of ovarian carcinomas, respectively. Positive cytoplasmic immunostaining of clone SPT24 was detected in 1.6% of cases. In contrast, normal ovarian tissue showed negative expression of both clones. A highly significant difference was observed between both clones regarding their sensitivity in ovarian carcinomas (P=0.004). A significant inverse relationship was observed between TTF-1 (SPT24 clone) expression and tumor stage (P=0.022). TTF-1 expression is not exclusive to lung and thyroid tissue. It is expressed in ovarian carcinomas where clone SPT24 is more sensitive than clone 8G7G3/1. TTF-1 might be of diagnostic utility in evaluating neoplasms of unknown primary origin as well as adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy. Moreover, TTF-1 expression might be a good prognostic factor in ovarian carcinoma.

Combined use of COX-1 and VEGF immunohistochemistry refines the histopathologic prognosis of renal cell carcinoma.

The course of RCC is asymptomatic, resulting in 25-30% of patients presenting with metastatic disease at time of diagnosis. The development of novel agents targeting angiogenesis and signal transduction pathways has improved patient outcomes. Role of cyclooxygenase in cancer development has been the subject of close scrutiny. COX-1 has been recognized to be involved in regulation of angiogenesis. To date, no immunohistochemical studies have been performed to assess the possible association between COX-1 and VEGF in RCC. This study is designed to evaluate the relationship between these two proteins in RCC. Also, the relationship between their combined immunohistochemical expression and different clinicopathological prognostic parameters in RCC is investigated. Immunohistochemical expression of COX-1 and VEGF was evaluated retrospectively on 64 cases of primary RCC including: 45 clear cell carcinoma, 12 papillary carcinoma and 7 of chromophope carcinoma. High COX-1 expression was detected in 62.5% of RCCs with a significant association with tumor grade (P=0.028), and highly significant relationship with tumor size and stage (P=0.001). There was a highly significant relationship between the VEGF score and tumor size (P=0.001), and stage (P=0.006). There was a positive correlation between COX-1 and VEGF expression score (P=0.001). Combined expression of both markers predicts high stage tumors (stage III/IV). Immunohistochemical expression of COX-1 and VEGF is associated with poor prognostic parameters in RCC. Their combined expression has a beneficial role in prediction of high stage tumors (III/IV).

Relationship between osteopontin and ß-catenin immunohistochemical expression and prognostic parameters of colorectal carcinoma.

Previous studies on the prognostic value of osteopontin (OPN) and ß-catenin in colorectal carcinoma (CRC) revealed conflicting results. To date, only two immunohistochemical studies investigated their association in CRC with discrepant results. Moreover, the relevance of their co-expression to clinicopathological parameters was not previously reported. This study was designed to investigate the relationship between these markers and prognostic parameters in CRC and study further the relationship between them. Immunohistochemical expression of OPN and ß-catenin was evaluated in 72 CRCs. Cytoplasmic OPN was detected in 45.83% of CRCs while normal mucosa was immunonegative. Strong continuous membranous ß-catenin was present in normal mucosa. However, abnormal membranous, nuclear and cytoplasmic expressions were observed in 36.11%, 31.94% and 52.78% of CRCs, respectively. A highly significant relationship was detected between each of OPN and nuclear ß-catenin expression and lymph node metastasis (P = 0.0001 and 0.004 respectively), depth of invasion (P = 0.001 and 0.004 respectively), TNM stages (P = 0.0001 and 0.001 respectively) and Dukes' stages (P = 0.0001 and 0.004 respectively). A significant association was found between OPN and distant metastases. A strong agreement was observed between OPN and nuclear ß-catenin (kappa = 0.656). A highly significant relationship was found between their co-expression and poor prognostic parameters. OPN overexpression and nuclear ß-catenin expression appeared to be associated with unfavorable prognostic factors in CRC. A direct relationship was observed between them. Further understanding their role in colorectal carcinogenesis as well as targeting the interaction between them might be effective in the future development of therapeutic agents for CRC patients.

Immunohistochemical expression of CD117 and vascular endothelial growth factor in retinoblastoma: possible targets of new therapies.

CD117 (C-kit) is thought to play an important role in tumourigenesis. There are limited data in the literature concerning C-kit expression in retinoblastoma. To date, no immunohistochemical studies have been performed to assess the possible association of C-kit with vascular endothelial growth factor (VEGF) in retinoblastoma. This study was designed to investigate C-kit and VEGF immunoexpression in retinoblastoma, their relationship with prognostic parameters as well as the correlation between them. A prospective immunohistochemical study was conducted on 56 retinoblastoma cases. Patients who had received preoperative chemotherapy were excluded. Positive C-kit and VEGF immunoreactivity was observed in 48.2% and 76.8% of retinoblastoma cases respectively. No C-kit immunostaining was seen in the adjacent uninvolved retina. However, VEGF expression was detected within its vasculature. Retinoblastomas with combined pattern of tumour growth revealed a highly significant positive C-kit expression (P = 0.002) compared to cases with endophytic or exophytic growths. Also, positive C-kit expression was statistically higher in cases with optic nerve invasion (P = 0.001) and choroidal invasion (P ≤ 0.01) compared to negative cases. A highly significant positive VEGF expression was detected in cases with optic nerve invasion (P = 0.013) compared to negative cases. Moreover, a highly significant positive correlation was detected between C-kit and VEGF expression (P = 0.006). C-kit is a feature of more aggressive retinoblastomas, with increased expression in tumours spreading beyond the retina. Moreover, VEGF is vastly expressed in retinoblastoma and is associated with optic nerve invasion. Both C-kit and VEGF may represent potential therapeutic targets for retinoblastomas.

Immunohistochemical expression of survivin in breast carcinoma: relationship with clinicopathological parameters, proliferation and molecular classification.

BACKGROUND AND OBJECTIVE: Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinicopathological parameters, proliferation (MIB-1) and molecular classification MATERIAL AND METHODS: Our retrospective study comprised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immunostained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. RESULTS: Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immunonegative. Survivin expression showed significant association with increased tumor size (p<0.0001), high histologic grade (p=0.04), lymph node metastases (p<0.001), advanced tumor stage (p<0.0001), MIB-1 expression (p=0.02), negative estrogen receptor status (p=0.01) and negative progesterone receptor status (p<0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes (p=0.01). CONCLUSION: Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel cancer treatment. KEY WORDS: Breast carcinoma - Immunohistochemistry - MIB-1 - Molecular classification - Survivin.