Discrimination of p53 immunohistochemistry-positive tumors by its staining pattern in gastric cancer

Immunohistochemistry staining of p53 is a cheap and simple method to detect aberrant function of p53. However, there are some discrepancies between the result of immunohistochemistry staining and mutation analysis. This study attempted to find a new definition of p53 staining by its staining pattern. Immunohistochemistry staining of p53 and TP53 gene mutation analysis were performed in 148 gastric cancer patients. Also SNP‐CGH array analysis was conducted to four cases. Positive staining of p53 was observed in 88 (59.5%) tumors. Tumors with positive p53 staining showed malignant features compared to negative tumors. Mutation of TP53 gene was observed in 29 (19.6%) tumors with higher age and differentiated type. In positive p53 tumors, two types could be distinguished; aberrant type and scattered type. With comparison to TP53 gene mutation analysis, all the scattered type had wild‐type TP53 gene (P = 0.0003). SNP‐CGH array showed that scattered‐type tumors had no change in the structure of chromosome 17. P53‐scattered‐type staining tumors may reflect a functionally active nonmutated TP53 gene. In interpretation of p53 immunohistochemistry staining, distinguishing p53‐positive tumors by their staining pattern may be important in gastric cancer.

[1]  E. Oki,et al.  Mortalin is a prognostic factor of gastric cancer with normal p53 function , 2014, Gastric Cancer.

[2]  胃癌研究会.  Japanese classification of gastric carcinoma , 1995 .

[3]  K. Gunderson,et al.  High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping. , 2006, Genome research.

[4]  K. Murakami,et al.  Analysis of p53 gene mutations in Helicobacter pylori-associated gastritis mucosa in endoscopic biopsy specimens. , 1999, Scandinavian journal of gastroenterology.

[5]  W. Bodmer,et al.  p53 mutations in colorectal cancer. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Levine,et al.  The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation , 1992, Cell.

[7]  D. Kirsch,et al.  Tumor-suppressor p53: implications for tumor development and prognosis. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. , 1991, Cancer research.

[9]  B. Vogelstein,et al.  An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms , 1994, The Journal of pathology.

[10]  B. C. Wong,et al.  Helicobacter pylori infection and gastric cancer. , 1999, Hong Kong medical journal = Xianggang yi xue za zhi.

[11]  C. Fenoglio-Preiser,et al.  TP53 and gastric carcinoma: A review , 2003, Human mutation.

[12]  C. Harris,et al.  The IARC TP53 database: New online mutation analysis and recommendations to users , 2002, Human mutation.

[13]  Yong Li,et al.  Prognostic value of expression of Kit67, p53, TopoIIa and GSTP1 for curatively resected advanced gastric cancer patients receiving adjuvant paclitaxel plus capecitabine chemotherapy. , 2012, Hepato-gastroenterology.

[14]  L. Messerini,et al.  Immunohistochemical vs molecular biology methods. Complementary techniques for effective screening of p53 alterations in head and neck cancer. , 1997, American journal of clinical pathology.

[15]  J. Blaydes,et al.  Stepwise transformation of primary thyroid epithelial cells by a mutant Ha‐ras oncogene: An in vitro model of tumor progression , 1992, Molecular carcinogenesis.

[16]  A. R. Gonçalves,et al.  Prognostic Significance of p53 Protein Expression in Early Gastric Cancer , 2011, Pathology & Oncology Research.

[17]  E. Tokunaga,et al.  Genetic mutual relationship between PTEN and p53 in gastric cancer. , 2005, Cancer letters.

[18]  A. Walch,et al.  Staining patterns of p53 immunohistochemistry and their biological significance in colorectal cancer , 2000, The Journal of pathology.

[19]  E. Oki,et al.  p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: Results in Japan and comparisons with other countries , 2007, Cancer science.

[20]  M. Washington,et al.  Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family. , 2008, Gastroenterology.

[21]  T. Mitsudomi,et al.  Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  A. Egashira,et al.  Overexpression of Hypoxia-Inducible Factor 1α and p53 Is a Marker for an Unfavorable Prognosis in Gastric Cancer , 2006, Clinical Cancer Research.

[23]  J. Benhattar,et al.  p53 Gene alterations and p53 protein accumulation in infiltrating ductal breast carcinomas: correlation between immunohistochemical and molecular biology techniques. , 1994, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[24]  Y. Maehara,et al.  Unregulated emissions from catalyst-equipped cars: EPA overview. , 1975, British Journal of Cancer.

[25]  F. Collins,et al.  Mutations in the p53 gene occur in diverse human tumour types , 1989, Nature.

[26]  T. A. Nagy,et al.  Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. , 2010, Gastroenterology.

[27]  S. Kato,et al.  Understanding the function–structure and function–mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[29]  I. Shih,et al.  Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis , 2011, Modern Pathology.

[30]  Takeshi Azuma,et al.  Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium , 2007, Nature Medicine.

[31]  M. Morita,et al.  Copy-Neutral Loss of Heterozygosity at the p53 Locus in Carcinogenesis of Esophageal Squamous Cell Carcinomas Associated with p53 Mutations , 2011, Clinical Cancer Research.

[32]  E. Oki,et al.  The Difference in p53 Mutations between Cancers of the Upper and Lower Gastrointestinal Tract , 2009, Digestion.

[33]  Japanese Gastric Cancer Association.  Japanese classification of gastric carcinoma: 3rd English edition , 2011, Gastric Cancer.

[34]  Xin Lu,et al.  Live or let die: the cell's response to p53 , 2002, Nature Reviews Cancer.

[35]  J. Lafitte,et al.  Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. , 2001, The European respiratory journal.

[36]  S. Lowe,et al.  Tumor suppression by Ink4a-Arf: progress and puzzles. , 2003, Current opinion in genetics & development.

[37]  R. Elledge,et al.  p53 protein accumulation detected by five different antibodies: relationship to prognosis and heat shock protein 70 in breast cancer. , 1994, Cancer research.

[38]  M. Asaka,et al.  Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma , 2003, Oncogene.

[39]  D. Lane,et al.  p53 In tumour pathology: Can we trust immunohistochemistry?—revisited! , 1994, The Journal of pathology.