PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India

A retrospective study

Thejaswini Venkatesh, Abhishek Shetty, Shrijeet Chakraborti, Padmanaban S. Suresh

Research output: Contribution to journalArticle

Abstract

Protein Tyrosine Phosphatase H1/Protein Tyrosine Phosphatase Non receptor Type 3 (PTPH1/PTPN3) is upregulated and/or mutated in glioma, ovarian, gastric, and colorectal cancers. Previous studies have documented that PTPH1-associated breast cancers exhibit enhanced sensitivity to tamoxifen and tyrosine kinase inhibitors through dephosphorylation of ER and epidermal growth factor receptor, respectively. Owing to the key role that PTPH1 plays as a biomarker in predicting the response of chemotherapeutic drugs and lack of studies on Indian breast cancer patients, the present study investigated PTPH1 protein expression and its relationship to clinical features, ER/PR/HER2/neu statuses, and methylation of promoter in breast cancer tissues (n = 67) among Indian population by immunohistochemistry and methylation specific polymerase chain reaction. PTPH1 expression was upregulated in 58.21% (39/67) and downregulated in the rest of tumor specimens, and it correlated with ER, PR, and HER2/neu statuses with p values of <0.0001, 0.0113, and 0.0448, respectively. Additionally, we found that the 2 kb region upstream of PTPH1 gene harbored CpG sites within, and was ubiquitously methylated in breast cancer (n = 13), colon cancer tissue (n = 1), uterine cancer tissue (n = 1), normal breast tissue (n = 1) in addition to Hela and MCF7 cell lines. In conclusion, our data showed a strong correlation of the PTPH1 status with the ER and ubiquitous nature of PTPH1 promoter methylation at specific CpG sites irrespective of cancer types and protein expression. Our findings underscore the clinical relevance of PTPH1 expression in Indian patients and warrant additional studies to explore the importance of ubiquitously methylated promoter at specific CpG sites in upstream of the PTPH1 gene.

Original languageEnglish
Pages (from-to)1071-1079
Number of pages9
JournalJournal of Cellular Physiology
Volume234
Issue number2
DOIs
Publication statusPublished - 01-02-2019

Fingerprint

Methylation
Non-Receptor Type 3 Protein Tyrosine Phosphatase
India
Retrospective Studies
Tissue
Breast Neoplasms
Genes
Uterine Neoplasms
Polymerase chain reaction
MCF-7 Cells
Biomarkers
Tamoxifen
HeLa Cells
Epidermal Growth Factor Receptor
Glioma
Ovarian Neoplasms
Protein-Tyrosine Kinases
Colonic Neoplasms
Stomach Neoplasms
Tumors

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

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title = "PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India: A retrospective study",
abstract = "Protein Tyrosine Phosphatase H1/Protein Tyrosine Phosphatase Non receptor Type 3 (PTPH1/PTPN3) is upregulated and/or mutated in glioma, ovarian, gastric, and colorectal cancers. Previous studies have documented that PTPH1-associated breast cancers exhibit enhanced sensitivity to tamoxifen and tyrosine kinase inhibitors through dephosphorylation of ER and epidermal growth factor receptor, respectively. Owing to the key role that PTPH1 plays as a biomarker in predicting the response of chemotherapeutic drugs and lack of studies on Indian breast cancer patients, the present study investigated PTPH1 protein expression and its relationship to clinical features, ER/PR/HER2/neu statuses, and methylation of promoter in breast cancer tissues (n = 67) among Indian population by immunohistochemistry and methylation specific polymerase chain reaction. PTPH1 expression was upregulated in 58.21{\%} (39/67) and downregulated in the rest of tumor specimens, and it correlated with ER, PR, and HER2/neu statuses with p values of <0.0001, 0.0113, and 0.0448, respectively. Additionally, we found that the 2 kb region upstream of PTPH1 gene harbored CpG sites within, and was ubiquitously methylated in breast cancer (n = 13), colon cancer tissue (n = 1), uterine cancer tissue (n = 1), normal breast tissue (n = 1) in addition to Hela and MCF7 cell lines. In conclusion, our data showed a strong correlation of the PTPH1 status with the ER and ubiquitous nature of PTPH1 promoter methylation at specific CpG sites irrespective of cancer types and protein expression. Our findings underscore the clinical relevance of PTPH1 expression in Indian patients and warrant additional studies to explore the importance of ubiquitously methylated promoter at specific CpG sites in upstream of the PTPH1 gene.",
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PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India : A retrospective study. / Venkatesh, Thejaswini; Shetty, Abhishek; Chakraborti, Shrijeet; Suresh, Padmanaban S.

In: Journal of Cellular Physiology, Vol. 234, No. 2, 01.02.2019, p. 1071-1079.

Research output: Contribution to journalArticle

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