OBJECTIVETo explore the biomarkers of early diagnosis in patients with polycyclic aromatic hydrocarbons (PAHs)-related lung cancer for the application to detection of occupational lung cancer or related lung cancer.

METHODSWestern dot blotting was used to explore the expression of ras, p53 and heat stress protein 70 (HSP70) in 29 patients with PAHs-related lung cancer (LC), and 28 patients with non-cancerous pulmonary disease, and 30 healthy controls.

RESULTSThe positive detection rates of P21, P53, and HSP70 in LC group (58.62%, 34.48%, 41.38% respectively) were higher than those in non-cancerous pulmonary disease group (14.29%, 7.14%, 10.71% respectively, P < 0.01). The sensitivity of P21, P53 and HSP70 were 58.62%, 34.48% and 41.38% respectively, negative predictive value (NPV) were 68.42%, 78.05% and 63.04% respectively. The co-detection of the three proteins mentioned above produced a sensitivity of 82.76% with a NPV of 78.26% (P < 0.05). Of 18 cases of LC with negative cytology, 13 (72.22%) were found HSP21, P53 or HSP70 positive.

CONCLUSIONSCo-detection of the P21, P53, and HSP70 may be used as the screening marker for diagnosis of PAHs-related lung cancer, and may supplement the diagnostic value of conventional cytology.

Aged ; Biomarkers ; analysis ; Blotting, Western ; Case-Control Studies ; HSP70 Heat-Shock Proteins ; analysis ; Humans ; Lung Neoplasms ; chemically induced ; metabolism ; pathology ; Middle Aged ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; poisoning ; Proto-Oncogene Proteins p21(ras) ; analysis ; Tumor Suppressor Protein p53 ; analysis

The p21 overexpression is thought to be a consequence of the p53 induced activation of the p21 gene. The immunohistochemical evaluation of p53 and p21 can be a valuable means of assessing the functional status of the p53 gene product. We examined the overexpression of p21 and p53 proteins in primary gastric lymphomas and the correlation with prognosis. A total of 32 cases of gastric lymphomas was classified into low-grade lymphomas of mucosa-associated lymphoid tissue type (n=16) and high-grade B-cell lymphomas (n=16). In low-grade lymphomas, only one case showed p53 positivity and all cases were p21-negative. In high-grade lymphomas, seven cases were p53+/p21- (44%), one case was p53+/p21+ (6%), and eight cases were p53-/p21- (50%). The p53+/p21- cases had a much lower percentage of patients sustaining a continuous complete remission state (3/7, 43%) compared with other cases (6/7, 86%). From these results, we concluded that p21 expression is rare in primary gastric lymphomas. Therefore, p53-positive lymphomas can be assumed as having p53 mutation. And combined studies of p53 and p21 may be used as a prognostic indicator in primary gastric high-grade lymphomas.
Adult ; Aged ; Antibodies, Monoclonal ; Female ; Human ; Immunohistochemistry ; Lymphoma, B-Cell/*chemistry/pathology ; Male ; Middle Age ; Peyer's Patches/chemistry/pathology ; Prognosis ; Protein p53/*analysis/immunology ; Proto-Oncogene Protein p21(ras)/*analysis/immunology ; Stomach Neoplasms/*chemistry/pathology ; Support, Non-U.S. Gov't

BACKGROUND: Cyclin-dependent kinase inhibitors (CDKI), including p21, p27 and p57 of the KIP family, are negative regulators of cell cycle progression and potentially act as tumor suppressors. The expression of p21 is induced by tumor suppressor gene p53. Mutations of p53 are common and found in various human cancers. Thus, the function of p21 as a tumor suppressor may be not retained after p53 mutation in human cancers. The aim of our study was to evaluate the tumor suppressive activity of p21 and p53 in human gastric cancer. METHODS: One hundred and two patients who underwent surgery for gastric cancer at Chonnam National University Hospital were selected retrospectively for this study. The primary selection criteria were the availability of formalin-fixed and paraffin-embedded blocks and sufficient clinical follow-up for tumor-specific survival analysis. In this study, we examined the expression of p21 and p53 in human gastric cancer tissue by immunohisto-chemistry and the correlation between their expression and clinicopathological variables. RESULTS: p21 and p53 immunoreactivities were localized in the nuclei of carcinoma cells. Positive nuclear expression of p21 and p53 was demonstrated in 63.7 and 33.3% of cancer tissues, respectively. No apparent correlation was noted between p21 and p53 expression. Negative expression of p21 correlated with advanced stage and lymph node metastasis (p=0.028 and 0.017, respectively). Moreover, negative expression of p21 correlated with poor survival (p=0.037). Positive expression of p53 correlated with depth of tumor invasion (p=0.029). However, no significant correlation could be observed between the status of p53 expression and survival. Combined analysis of p21 and p53 status showed that p21 negative and p53 positive tumors had a poorer survival than other group tumors (p=0.026). CONCLUSION: These results suggest that the status of p21 and p53 expression may help in predicting the aggressive behavior of gastric cancer. However, further studies are warranted to clarify the impact of p53 on the function of p21 as a tumor suppressor.
Adult ; Aged ; Carcinoma/genetics/*metabolism ; Female ; Gene Expression ; Genes, p53 ; Human ; Male ; Middle Aged ; Oncogene Protein p21 (ras) /genetics/*metabolism ; Prognosis ; Protein p53/genetics/*metabolism ; Retrospective Studies ; Stomach Neoplasms/genetics/*metabolism ; Survival Analysis ; Tumor Markers, Biological/genetics/*metabolism

The clinical, radiological and pathologic features of a biphasic synovial sarcoma in the left elbow joint of a two-year-old male Rottweiler are presented. The tumor showed positive immunoreactivity for vimentin, Epithelial Membrane Antigen (EMA), p53 and PCNA, while it was negative for the cytokeratin used, S-100, Rb and p21. Immunohistochemistry for EMA allowed the identification of epithelioid components of synovial sarcoma, and may, therefore, contribute in establishing a diagnosis of biphasic synovial sarcoma. Intratumoral variation in PCNA immunoreactivity was minimal, indicating that the various tumor components proliferate at more or less similar rates. Overall, the characterized immunohistochemical profile for canine synovial sarcoma, not defined previously, may provide clues to the histogenesis of the phenotypically mesenchymal and epithelial elements of the tumor, and may be of value in the differential diagnosis of challenging cases, decreasing the risk of under- and mis-diagnosis. Although more cases need to be studied to determine whether there is a consistent pattern of immunostaining in canine synovial sarcoma, its potential significance is discussed in relation to the histogenesis, molecular pathology and differential diagnosis of canine synovial sarcoma.
Animals ; CA-15-3 Antigen/analysis ; Dog Diseases/*pathology/radiography ; Dogs ; Elbow Joint/abnormalities/pathology/radiography ; Forelimb ; Histocytochemistry/veterinary ; Immunohistochemistry/veterinary ; Keratins/analysis ; Male ; Oncogene Protein p21(ras)/analysis ; Proliferating Cell Nuclear Antigen/analysis ; Retinoblastoma Protein/analysis ; Sarcoma, Synovial/chemistry/pathology/radiography/*veterinary ; Soft Tissue Neoplasms/chemistry/radiography/*veterinary ; Tumor Suppressor Protein p53/analysis ; Vimentin/analysis

OBJECTIVETo analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions.

METHODSFifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing.

RESULTS(1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50).

CONCLUSIONSImmunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenocarcinoma ; genetics ; metabolism ; Adenoma ; genetics ; metabolism ; Aged ; Class I Phosphatidylinositol 3-Kinases ; Colonic Polyps ; genetics ; metabolism ; Colorectal Neoplasms ; genetics ; metabolism ; DNA Mismatch Repair ; DNA Modification Methylases ; metabolism ; DNA Repair Enzymes ; metabolism ; DNA, Neoplasm ; metabolism ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Hyperplasia ; Immunophenotyping ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; metabolism ; Nuclear Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; genetics ; Point Mutation ; Precancerous Conditions ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins B-raf ; genetics ; Proto-Oncogene Proteins p21(ras) ; Sequence Analysis, DNA ; Tumor Suppressor Proteins ; metabolism ; ras Proteins ; genetics