Elsevier

Pathophysiology

Volume 24, Issue 2, June 2017, Pages 99-106
Pathophysiology

Original research article
Immunohistochemical analysis of PTEN, HER2/neu, and ki67 expression in patients with gastric cancer and their association with survival

https://doi.org/10.1016/j.pathophys.2017.02.006Get rights and content

Abstract

Background

Considering the poor prognosis of patients with gastric cancer, molecular diagnostic and prognostic markers for this cancer should be established. The aims of our study were to assess the correlations between PTEN, HER2/neu, and Ki67 expressions and clinicopathological factors of gastric cancer patients in upper Egypt, as well as their influence on OS and DFS.

Patients and methods

In this descriptive-analytic study, 42 patients with gastric carcinoma treated by postioerative chemoradiation between 2004 and 2014. Pathological review was done. Immunohistochemical staining and evaluation were performed.

Results

All the studied markers were significantly correlated with increased TNM stage. Her2/neu overexpression and positive Ki67 expression were significantly associated with histological grade. High percentage of positive Her2/neu and Ki67expression was found in gastric carcinoma tissue samples which lack PTEN expression. The one-year OS rate for the entire group (n = 42) was 77.4%, whereas the DFS rate was 45%. Pathological T stage PTEN status significantly affected both OS (p = 0.029 and 0.027 respectively) and DFS (p = 0.006 and 0.012 respectively) rates. Multivariate Cox analyses showed that only pathological T stage was an independent prognostic factor affecting OS (P = 0. 007, HR: 2.02; 95% CI: 1.2–3.38)and DFS(P < 0.0001, HR: 2.69; 95% CI: 1.54–4.69).

Conclusion

All the studied molecular markers, was significantly correlated with pathological T stage that significantly affected both OS and DFS rates. These findings indicate that these markers have an important role in gastric cancer growth and dissemination so these markers can be used as a prognostic biomarker. In addition, therapies targeting Her2 and PTEN may help develop novel therapeutics for gastric cancer.

Section snippets

Background

Gastric cancer is the fourth most commonly diagnosed cancer and the second most common cause of cancer related death worldwide [1]. In Egypt, Gastric cancer is the 12th most common cancer in both sexes representing 1.6% of the total cancers and it is reported to be the 12th leading cause of cancer death representing 2.2% of the total cancer mortality [2]. The 5-year survival rate of patients with gastric carcinoma is actually less than 20% as most patients are diagnosed with advanced disease at

Patients and materials

In this descriptive-analytic study, our sample comprised 42 patients who were biopsied, diagnosed and underwent potentially curative surgery for gastric carcinoma at the Assuit university hospital, Assuit and received postoperative chemoradiation between January 2004 and January 2014. Clinicopathological data, including gender, age at diagnosis, clinical performance, histological type, histological grade, depth of invasion, lymph node metastasis, distant metastasis and clinical follow-up

Clinicopathological findings

Of the 42 gastric carcinoma patients, 61.9% (n = 26) were males and 38.1% (n = 16) were females. Their mean age was 53 years (range: 35–80). 15 (35.7%) of cases were with clinical performance I, 19 (45.2%) were with clinical performance II and 8 (19%) were with clinical performance III. In histopathologic examination, 25 (59.5%) of cases were of the intestinal type, 9 (21.4%) of cases were of the diffuse type and 8 (19%) of cases were of the mixed type of gastric carcinoma. With regard to the

Discussion

Most gastric cancer patients are diagnosed with advanced disease with the development of distant metastases [3]. Regarding the difficulty of treatment and the dismal prognosis of patients with metastatic diseases, assessment of prognostic markers in these patients should be done. Although gastric cancer represents one of the leading causes of death in Egypt, only one recent reported study [19] was done one molecular marker affecting gastric cancer in Egyptian patients. The present study

Conclusion

The incidence of gastric cancer was increased in the last 10 years in upper Egypt and few studies were done to study molecular markers which affect mechanisms of its carcinogenesis, spreading, prognosis and survival of these patients. This is the first study in Egypt to discuss the effect of combining more than one molecular event in the prognostication process in gastric carcinoma.

In our study all the studied molecular markers, were significantly correlated with increased TNM stage, and

Conflict of interest

The authors declare that they have no conflict of interests

Funding

The authors received no financial or other support for the research reported in this manuscript.

Acknowledgement

Not applicable.

References (29)

  • D.J. Slamon et al.

    Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer

    Science

    (1989)
  • A. Lazarev et al.

    [Ki-67 and p53 expression in gastric dysplasias and cancer]

    Arkh. Patol.

    (2005)
  • G. Aune et al.

    The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may contribute in the identification of aggressive ovarian carcinomas

    Int. J. Clin. Exp. Path.

    (2011)
  • K. Washington

    of the AJCC cancer staging manual: stomach

    Ann. Surg. Oncol.

    (2010)

    • Cited by (0)

    View full text
    © 2017 Elsevier B.V. All rights reserved.