Loss of RKIP expression during the carcinogenic evolution of endometrial cancer

Martinho, Olga; Faloppa, Carlos Chaves; Scapulatempo‐Neto, Cristovam; Longatto‐Filho, Adhemar; Baiocchi, Glauco; Cunha, Isabela Werneck da; Soares, Fernando Augusto; Fregnani, José Humberto Tavares Guerreiro; Reis, Rui Manuel

doi:10.1136/jclinpath-2011-200358

Cited by 24 publications

(20 citation statements)

References 51 publications

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“…Tissue microarray (TMA) slides with 3 µm-thick sections were subjected to immunohistochemical analysis according to the streptavidinbiotin peroxidase complex system (UltraVision Large Volume Detection System Anti-Polyvalent, HRP; LabVision Corporation, CA, USA), as previously described (27,30,39). Briefly, deparaffinised and rehydrated slides were submitted to heat-induced antigen retrieval for 20 min at 98˚C with 10 mM citrate buffer (pH 6.0).…”

Section: Methodsmentioning

confidence: 99%

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Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

et al. 2012

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Abstract. Gastric cancer is a leading cause of cancer-related mortality, and the presence of lymph node metastasis an important prognostic factor. Downregulation of RKIP has been associated with tumor progression and metastasis in several types of neoplasms, being currently categorized as a metastasis suppressor gene. Our aim was to determine the expression levels of RKIP in gastric tissues and to evaluate its impact in the clinical outcome of gastric carcinoma patients. RKIP expression levels were studied by immunohistochemistry in a series of gastric tissues. Overall, we analysed 222 non-neoplastic gastric tissues, 152 primary tumors and 42 lymph node metastasis samples. We observed that RKIP was highly expressed in ~83% of non-neoplastic tissues (including normal tissue and metaplasia), was lost in ~56% of primary tumors and in ~90% of lymph node metastasis samples. Loss of RKIP expression was significantly associated with several markers of poor clinical outcome, including the presence of lymph node metastasis. Furthermore, the absence of RKIP protein constitutes an independent prognostic marker for these patients. In conclusion, RKIP expression is significantly lost during gastric carcinoma progression being almost absent in lymph node metastasis samples. Of note, we showed that the absence of RKIP expression is associated with poor outcome features of gastric cancer patients, this being also an independent prognostic marker.

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Section: Methodsmentioning

confidence: 99%

“…For negative controls, primary antibodies were omitted and also replaced by a universal negative control antibody (CEA, rabbit anti-human, Dako Corporation, Carpinteria, CA, USA). Prostate carcinoma and GISTs cases, previously analysed (27,30,39), were used as positive and negative controls. Statistical analysis.…”

Section: Methodsmentioning

confidence: 99%

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

et al. 2012

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“…Representative 3-μm-thick tissue sections were used for immunohistochemical analysis according to the streptavidin-biotin-peroxidase complex system (UltraVision Large Volume Detection System Anti-Polyvalent HRP; LabVision Corporation), as previously described [21,22,23,24,25]. Briefly, deparaffinized and rehydrated slides were submitted to heat-induced antigen retrieval for 20 min at 98°C with 10 m M citrate buffer (pH = 6.0).…”

Section: Methodsmentioning

confidence: 99%

“…The score used was the sum of the percentage of positive cells (0, negative; 1, less than 25% positive cells; 2, 26-50% positive cells; 3, more than 50% positive cells) and the staining intensity (0, negative; 1, weak; 2, moderate; 3, strong). Scores between 0 and 2 were classified as negative, 3 and 4 as moderately positive, and 5 and 6 as strongly positive [21,22,23,24,25]. …”

Section: Methodsmentioning

confidence: 99%

Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

et al. 2016

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Objective: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. Methods: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. Results: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. Conclusion: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.

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“…The level of SPINT2 staining was semi-quantitated by intensity scoring: 0, negative; 1, weak; 2, moderate; 3, strong (Bergum et al 2010;Martinho et al 2012;Martinho et al 2013). Tumor tissues that presented scores between 0 and 1 were classified as negative for SPINT2 staining, those that were scored as 2 demonstrated moderate positive staining, and those scoring 3 as strongly positive.…”

Section: Spint2 Immunohistochemistrymentioning

confidence: 99%

SPINT2 Deregulation in Prostate Carcinoma

Pereira

Almeida

Pinto

et al. 2015

J Histochem Cytochem.

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SummarySPINT2 is a tumor suppressor gene that inhibits proteases implicated in cancer progression, like HGFA, hepsin and matriptase. Loss of SPINT2 expression in tumors has been associated with gene promoter hypermethylation; however, little is known about the mechanisms of SPINT2 deregulation in prostate cancer (PCa). We aimed to analyze SPINT2 expression levels and understand the possible regulation by SPINT2 promoter hypermethylation in PCa. In a cohort of 57 cases including non-neoplastic and PCa tissues, SPINT2 expression and promoter methylation was analyzed by immunohistochemistry and methylation-specific PCR, respectively. Methylation status of the SPINT2 promoter was also evaluated by bisulfite sequencing and 5-aza-2'-deoxycytidine treatment. Oncomine and TCGA databases were used to perform in silico PCa analysis of SPINT2 mRNA and methylation levels. A reduction in SPINT2 expression levels from nonneoplastic to PCa tissues was observed; however, none of the cases exhibited SPINT2 promoter methylation. Both bisulfite sequencing and 5-aza demonstrated that SPINT2 promoter is not methylated in PCa cells. Bioinformatics approaches did not show downregulation of SPINT2 at the mRNA level and, in corroboration with our results, SPINT2 promoter region is reported to be unmethylated. Our study suggests an involvement of SPINT2 in PCa tumorigenesis, probably in association with a post-translational regulation of SPINT2. (J Histochem Cytochem 64:32-41, 2016)

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Loss of RKIP expression during the carcinogenic evolution of endometrial cancer

Cited by 24 publications

References 51 publications

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Absence of RKIP expression is an independent prognostic biomarker for gastric cancer patients

Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

SPINT2 Deregulation in Prostate Carcinoma

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