Nyagol Joshua, Nyong'o Aggrey, Byakika Bessie, Muchiri Lucy, Cocco Mario, de Santi M M, Spina Donatella, Bellan Cristiana, Lazzi Stefano, Kostopoulos Ioannis, Luzi Pietro, Leoncini Lorenzo
Department of Human Pathology and Oncology, University of Siena, Italy.
Anal Quant Cytol Histol. 2006 Apr;28(2):97-103.
To report the expression of estrogen receptors, progesterone receptors and human epidermal growth factor receptor (Her-2/neu) in 158 Kenyan women with breast cancer and correlation with other prognostic indicators in this high-risk group. This study stressed the importance of routine assessment of the steroid receptors and Her-2/neu as a mode of therapeutic selection of patients for antihormonal or targeting monoclonal antibody (Herceptin) therapy, directed at the juxtamembrane domain of Her-2/neu protein in the developing countries such as Kenya.
The study population consisted of 158 female patients with histologically confirmed breast carcinoma seen at the pathology department of The Nairobi Hospital. An immunohistochemical (IHC) study of ER, PR and Her-2/neu was conducted, followed by fluorescent in situ hybridization (FISH) validation for Her-2/neu gene amplification in cases initially scored as positive 2+ with IHC. Mastectomy samples registered at the pathology department of The Nairobi Hospital were used for this study. The study was approved by the institution's ethical review committee and informed consent obtainedfrom the concerned patients.
In the studied cohort, positivity for both hormonal receptors and Her-2/neu was noted in 10 (6.33%) cases and negativity in 44 (27.85%) cases. Conversely, Her-2/neu negativity was noted in 32 (20.25%) cases with both steroid receptors positive and Her-2/neu positivity with both steroid receptors negative in 20 (12.66%) cases. Overall, no predictive factor was found in the Her-2/neu amplified 31/153 (20.26%) cases completely assessed with IHC and FISH. Grade III invasive ductal carcinomas, however, had a high prevalence of Her-2/neu overexpression. Association of both menopausal status (p = 0.044) and progesterone receptor status (p = 0.004) with high grade tumors were found to be statistically significant at 95% CI (p < 0.5). Consistent with other studies, Her-2/neu overexpression in this cohort was 20.26%.
Her-2/neu positivity may activate ER expression through signaling kinases, and the combined target of mitogenic estrogen plus the monoclonal antibody therapy against Her-2/neu-overexpressing tumors expand chances of survival for patients in developing countries such as Kenya. The cost factor for these tests, selection for appropriate combined therapies and lack of awareness were noted as limiting factors for access to basic health care service and resulted in advanced tumor grade at time of patient presentation.
报告158例肯尼亚乳腺癌女性患者中雌激素受体、孕激素受体及人表皮生长因子受体（Her-2/neu）的表达情况，并与该高危组中的其他预后指标进行相关性分析。本研究强调了在肯尼亚等发展中国家，常规评估类固醇受体和Her-2/neu作为抗激素或靶向单克隆抗体（赫赛汀）治疗患者治疗选择模式的重要性，该治疗针对Her-2/neu蛋白的近膜结构域。
研究人群包括在内罗毕医院病理科就诊的158例经组织学确诊的乳腺癌女性患者。对雌激素受体（ER）、孕激素受体（PR）和Her-2/neu进行了免疫组织化学（IHC）研究，随后对最初免疫组化评分为2+阳性的病例进行荧光原位杂交（FISH）验证Her-2/neu基因扩增情况。本研究使用在内罗毕医院病理科登记的乳房切除术样本。该研究获得了机构伦理审查委员会的批准，并获得了相关患者的知情同意。
在研究队列中，激素受体和Her-2/neu均为阳性的病例有10例（6.33%），均为阴性的病例有44例（27.85%）。相反，32例（20.25%）类固醇受体均为阳性的病例中Her-2/neu为阴性，20例（12.66%）类固醇受体均为阴性的病例中Her-2/neu为阳性。总体而言，在通过免疫组化和FISH完全评估的153例（20.26%）Her-2/neu扩增病例中未发现预测因素。然而，III级浸润性导管癌中Her-2/neu过表达的发生率较高。发现绝经状态（p = 0.044）和孕激素受体状态（p = 0.004）与高级别肿瘤的相关性在95%置信区间具有统计学意义（p < 0.5）。与其他研究一致，该队列中Her-2/neu过表达率为20.26%。
Her-2/neu阳性可能通过信号激酶激活雌激素受体表达，有丝分裂雌激素与针对Her-2/neu过表达肿瘤的单克隆抗体联合治疗的靶点，增加了肯尼亚等发展中国家患者的生存机会。这些检测的成本因素、合适联合治疗的选择以及认识不足被认为是获得基本医疗服务的限制因素，并导致患者就诊时肿瘤分级较高。
