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Alterations in p53, BRCA1, ATM, PIK3CA, and HER2 genes and their effect in modifying clinicopathological characteristics and overall survival of Bulgarian patients with breast cancer

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Abstract

Purpose

Though p53, BRCA1, ATM, PIK3CA, and HER2 genes are shown to be involved in various aspects of breast carcinogenesis, their functional relationship and clinical value are still disputable. We investigated the genetic status or expression profile of these genes to further elucidate their clinical significance.

Methods

PCR-SSCP-Sequencing of p53, BRCA1, ATM, and PIK3CA was performed in 145 Bulgarian patients with sporadic breast cancer. Expression profiles of HER2 were determined by ICH and CISH. Relationship between mutations and clinicopathological characteristics was evaluated by Chi-squared and Fisher’s exact tests. Multivariate Cox proportional hazard test and Kaplan–Meier analysis were used to evaluate differences in overall survival between groups.

Results

The frequency of p53 (22.07%), BRCA1 (0.69%), ATM (7.59%), and PIK3CA (31.25%) alterations and HER2 (21.21%) overexpression was estimated. Mutated p53 was associated with tumor size (P = 0.033) and grade of malignancy (P = 0.001), ATM—with grade of malignancy (P = 0.032), and PIK3CA—with PR-positive tumors (P = 0.047). HER2 overexpression correlated with age of diagnosis (P = 0.009), tumor size (P = 0.0004), and ER expression (P = 0.011). Univariate survival analysis showed that mutated p53 is an indicator for worse outcome (P = 0.041). Combination of two genetic abnormalities did not correlate with more aggressive carcinogenesis and worse overall survival.

Conclusions

Our data indicated that p53, BRCA1, ATM, PIK3CA, and HER2 alterations specifically correlate with clinicopathological characteristics of Bulgarian patients with breast cancer. Of these genes, only mutated p53 showed significant, though not independent, negative effect on overall survival.

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Abbreviations

BC:

Breast cancer

IHC:

Immunohistochemical analysis

CISH:

Chromogenic in situ Hybridization

OS:

Overall survival

T:

Tumor size

N:

Nodal status

G:

Grade of malignancy

ER:

Estrogen receptor

PR:

Progesterone receptor

HR:

Hazard ratio

CI:

Confidence interval

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Acknowledgments

Authors express their gratitude to Dr. Maria Nacheva who provided assistance in collecting of samples. We are grateful to Dr. Milka Georgieva for the critical reading of manuscript. This work was funded by the Bulgarian Ministry of Education and Science, projects No G-1-04/04 and DO 02.310/08.

Conflict of interest statement

We declare that we have no competing interests.

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Authors and Affiliations

  1. Institute of Genetics “Akad. Doncho Kostoff”, Department of Molecular Genetics, Bulgarian Academy of Sciences, “Plovdivsko shosse” 13 km., 1113, Sofia, Bulgaria

    Stefan S. Bozhanov, Svetla G. Angelova, Maria E. Krasteva, Tsanko L. Markov & Elena I. Georgieva

  2. Department of General and Clinical Pathology, Medical University, Sofia, Bulgaria

    Svetlana L. Christova

  3. National Oncological Centre Hospital, Sofia, Bulgaria

    Ivan G. Gavrilov

Authors
  1. Stefan S. Bozhanov
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  2. Svetla G. Angelova
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  3. Maria E. Krasteva
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  4. Tsanko L. Markov
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  5. Svetlana L. Christova
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  6. Ivan G. Gavrilov
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  7. Elena I. Georgieva
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Corresponding author

Correspondence to Elena I. Georgieva.

Additional information

Stefan S. Bozhanov and Svetla G. Angelova have contributed equally to this work.

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Bozhanov, S.S., Angelova, S.G., Krasteva, M.E. et al. Alterations in p53, BRCA1, ATM, PIK3CA, and HER2 genes and their effect in modifying clinicopathological characteristics and overall survival of Bulgarian patients with breast cancer. J Cancer Res Clin Oncol 136, 1657–1669 (2010). https://doi.org/10.1007/s00432-010-0824-9

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