High Frequency Of Overexpression Research Articles

P16 as a marker of carcinoma in effusions and peritoneal washing

BackgroundConsidering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68.ResultsP16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%.ConclusionOverexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.

Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

BackgroundHeterogeneous nuclear ribonucleoproteins (hnRNPs) of the A/B type (hnRNP A1, A2/B1, A3) are highly related multifunctional proteins participating in alternative splicing by antagonising other splicing factors, notably ASF/SF2. The altered expression pattern of hnRNP A2/B1 and/or splicing variant B1 alone in human lung cancer and their potential to serve as molecular markers for early diagnosis remain issues of intense investigation. The main objective of the present study was to use paired tumour/non-tumour biopsies from patients with non-small cell lung cancer (NSCLC) to investigate the expression profiles of hnRNP A1, A2/B1 and A3 in conjunction with ASF/SF2.MethodsWe combined western blotting of tissue homogenates with immunohistochemical examination of fixed tissue sections and quantification of mRNA expression levels in tumour versus adjacent normal-looking areas of the lung in the same patient.ResultsOur study, in addition to clear evidence of mostly uncoupled deregulation of hnRNPs A/B, has revealed hnRNP A1 to be the most deregulated protein with a high frequency of over-expression (76%), followed by A3 (52%) and A2/B1 (43%). Moreover, direct comparison of protein/mRNA levels showed a lack of correlation in the case of hnRNP A1 (as well as of ASF/SF2), but not of A2/B1, suggesting that different mechanisms underlie their deregulation.ConclusionOur results provide strong evidence for the up-regulation of hnRNP A/B in NSCLC, and they support the existence of distinct mechanisms responsible for their deregulated expression.

Epidermal growth factor receptor and c-erbB-2 oncoprotein expression in female genital tract carcinosarcomas (malignant mixed müllerian tumors). Clinicopathologic study of 82 cases.

Epidermal growth factor receptor (EGFR) and c-erbB-2 (also known as HER-2/neu) oncoprotein (p185erbB-2) are members of the subfamily of tyrosine kinase, transmembrane receptors often implicated in human carcinogenesis. We hypothesize that expression of EGFR and p185erbB-2 adds useful prognostic and histogenetic information regarding female genital tract carcinosarcomas (FGTCSs). Paraffin sections from 82 FGTCS (61 endometrium, 14 ovary, 5 cervix, and 2 fallopian tube), 56% of which exhibited heterologous elements, were stained using anti-EGFR (clone 31G7, Triton Diagnostics, Alameda, CA) and anti-p185erbB-2 (clone CB11, Novocastra Labs, UK). EGFR reactivity was present in 11 (13.4%) FGTCSs (55% carcinomatous component [CC] only, 18% sarcomatous component [SC] only, and 27% in both). EGFR was associated with adenosquamous histology of the CC (P < 0.05) and heterologous rhabdomyosarcomatous differentiation in the SC (P < 0.05); no other histopathologic features were correlated. p185erbB-2 reactivity was present in 79 (87.8% strong [S], 78% membrane [M], and 8.5% weak) FGTCSs (1% CC only, 0% SC only, and 99% in both). p185erbB-2 did not correlate with histopathologic features or EGFR. Seventy-seven patients had clinical follow-up for longer than 12 months. Approximately 49.3% and 72.3% of patients had recurrent disease by 12 and 80 months, respectively; all but 1 were dead from disease. 27% of patients were disease free after 15 to 307 months (median, 77 months; mean, 92 months). EGFR, but not p185erbB-2 expression predicted disease recurrence (P < 0.05). Recurrent disease was associated with Stage greater than I (P < 0.0001), vascular space invasion in resection specimens (P < 0.01), and deep myometrial invasion in hysterectomies (P < 0.05). EGFR was associated with Stage greater than I and did not help predict recurrence in good prognosis groups. p185erbB-2 overexpression in both CC and SC of FGTCS suggests a common carcinogenic mechanism for both components and supports the conversion-histogenesis hypothesis implicating a dominant role for the CC with the SC arising as a metaplastic change from the CC. EGFR may be expressed in either component and indicates aggressive biologic behavior; however, its prognostic utility is limited by its low predictive value for recurrence (40.3%), inability to foretell recurrence in good prognosis groups, and dependence on stage. High frequency of overexpression and dismal prognosis make FGTCS patients good candidates for trials of therapeutic strategies involving the p185erbB-2 receptor manipulations.