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. 2010 May 21:10:223.
doi: 10.1186/1471-2407-10-223.

Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study

Dalal M Al Tamimi  1 , Mohamed A Shawarby, Ayesha Ahmed, Ammar K Hassan, Amal A AlOdaini
Affiliations

Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study

Dalal M Al Tamimi et al. BMC Cancer. .

Abstract

Background: Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations.

Methods: We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out.

Results: Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p=0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2+(p=0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the tumor.

Conclusions: Subtyping by use of this immunohistochemical panel revealed a prevalence pattern that is unique to our population; luminal tumors comprised only 19.9%, and the unclassified group (penta negative) 42.8%, a distribution which is distinctive to our population and in contrast with all Western studies. The presence of a predominant unclassified group also suggests that the currently used molecular analytic spectrum may not completely encompass all molecular classes and there is a need to further refine and develop the existing classification systems.

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Figures

Figure 1
Figure 1
Tumor classification (original magnification × 200). a) Luminal A: ER strongly positive, PR positive or negative, HER2 negative, CK5/6 and EGFR negative. b) Luminal B: ER weakly to moderately positive and/or PR positive, HER2 negative, CK5/6 and EGFR negative. c) HER2: HER2 positive, ER and PR negative, CK5/6 and EGFR negative. d) Basal: CK5/6 and/or EGFR positive, ER and PR negative, HER2 negative. e) Unclassified (penta-ve): ER and PR negative, HER2 negative, CK5/6 and EGFR negative. f) Hybrid: co-positivity of different markers in varied combination, an example of HER2-Basal hybrid (HBH) is shown.
Figure 2
Figure 2
Prevalence of Molecular types of breast cancer compared to 4 large Western studies.
Figure 3
Figure 3
Prevalence of Molecular types of breast cancer compared to 2 large Asian and African studies.
See this image and copyright information in PMC

References

    1. Tarone RE. Breast cancer trends among young women in the United States. Epidemiology. 2006;17(5):588–590. doi: 10.1097/01.ede.0000229195.98786.ee. - DOI - PubMed
    1. Al-Kuraya K, Schramel P, Skeik, Amr S, Torhorst J, Tapia C, Novotny H, Spichtin H, Maurer R, Mirlacher M, Simon R, Sauter G. Predominance of high grade pathway in breast cancer development of middle east. Modern Pathology. 2005;18:891–897. doi: 10.1038/modpathol.3800408. - DOI - PubMed
    1. Registry NC. Cancer Incidence Report Saudi Arabia 2002. Riyadh. 2007.
    1. Ibrahim EM, al-Mulhim FA, al-Amri A, al-Muhanna FA, Ezzat AA, Stuart RK, Ajarim D. Breast cancer in the Eastern province of Saudi Arabia. Med Oncol. 1998;15(4):241–247. doi: 10.1007/BF02787207. - DOI - PubMed
    1. Ezzat AA, Ibrahim EM, Raja MA, Al-Sobhi S, Rostom A, Stuart RK. Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population. Med Oncology. 1999;16(2):95–103. doi: 10.1007/BF02785842. - DOI - PubMed

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