172例乳腺浸润性癌 HER -2免疫组化与 FISH 技术检验对比研究

目的：比较免疫组化（IHC）和荧光原位杂交（FISH）技术在检测乳腺浸润性癌患者中 HER -2蛋白表达和基因扩增的一致性。方法：分别用 IHC 和 FISH 技术对172例乳腺浸润性癌 HER -2进行蛋白表达和基因扩增检测,比较两者检测的结果和相关性。结果：172例浸润性乳腺癌标本行 IHC 检测结果30例为（1＋）,88例为（2＋）,42例为（3＋）,12例为（-）。172例乳腺癌标本进行 FISH 检测结果71例为阳性,101例为阴性。其中 FISH 结果阳性标本中 IHC 检测有2例（1＋）,30例（2＋）,39例（3＋）。IHC 检测 HER -2为（3＋）的病例 FISH 检测中阳性符合率92.9%（39/42）,且检测 HER -2（-）的病例 FISH 检测均为阴性, IHC 检测 HER -2（2＋）的88例患者中有58例经 FISH 检测证实 HER -2呈阴性,30例呈阳性。FISH 检测共发现47例17号染色体多体,其发生率为27.3%。用 IHC 检测 HER -2发现有25例标本存在肿瘤之间的不同表达,而在这25例标本的 FISH 检测结果中有11例存在 HER -2基因瘤内遗传异质性。结论：HER -2蛋白表达和基因扩增 IHC 和 FISH 检测在免疫组化强阳性的标本中具有较好的一致性,且免疫组化染色强度与HER -2基因扩增呈正相关。理解和判断 HER -2基因遗传异质性对肿瘤药物应用及 HER -2基因检测方法具有指导意义。     

IHC与FISH检测浸润性乳腺癌患者HER2蛋白表达和基因扩增的差异性分析

目的:探讨并比较免疫组织化学法（IHC）与荧光原位杂交法（FISH）检测浸润性乳腺癌人表皮生长因子受体-2（HER2）蛋白表达和基因扩增的差异性。方法:采用IHC法和FISH法分别检测桂西地区120例乳腺癌患者石蜡标本中HER2蛋白表达与基因扩增情况,比较IHC与FISH检测结果一致性并进行结果相关性分析。对检测不一致的病例重新检测及判读,分析差异原因。结果:120例乳腺癌患者中IHC 33例阳性（3+）中FISH检测阳性33例,阳性符合率100%;IHC 61例不确定（2+）中FISH检测阳性24例,阳性符合率39.34%;IHC 26例阴性（0/1+）中FISH检测阴性21例,阴性符合率80.77%。结果显示,除IHC（2+）外,IHC检测HER2蛋白表达与FISH检测HER2基因扩增有较好的一致性（P＜0.05）。造成两种检测方法差异的原因可能有标本固定不及时,抗体浓度偏低等。结论:IHC法检测HER2与FISH法一致性较好。临床实践中可根据实际情况,结合使用,以便指导临床治疗。     

荧光原位杂交和免疫组织化学法检测乳腺浸润性导管癌中HER-2基因状态的研究

目的 比较荧光原位杂交（FISH）和免疫组织化学（IHC）两种方法检测乳腺浸润性导管癌人类表皮生长因子受体2（HER-2）基因扩增及与C-erbB-2蛋白表达结果的一致性。方法 分别采用FISH和IHC法检测346例乳腺浸润性导管癌组织HER-2基因扩增和C-erbB-2蛋白表达,并对两种方法的结果进行统计学分析。结果 346例乳腺浸润性导管癌中,FISH检测HER-2基因扩增145例（41.9％）,无扩增201例（58.1％）。IHC检测显示,C-erbB-2蛋白（-）7例,（+）30例,（++）227例,（+++）82例。按乳腺癌HER-2检测指南,（-）和（+）为阴性结果,（+++）为阳性结果,（++）为不确定病例。全组IHC检测C-erbB-2蛋白阳性表达率为23.7％（82／346）。IHC检测C-erbB-2蛋白（-）的7例患者经FISH检测无HER-2基因扩增,一致率为100.0％。IHC检测C-erbB-2蛋白（+）的30例经FISH检测25例无基因扩增,一致率为83.3％;227例（++）中有65例基因扩增,一致率为28.6％;82例（+++）中有基因扩增75例,一致率为91.5％。IHC和FISH检测HER-2状态的一致率为89.9％,具有高度一致性（Kappa值=0.768,P＜0.001）。HER-2基因扩增与年龄、肿瘤大小、组织学分级及淋巴结转移均无关（P＞0.05）。结论IHC和FISH法检测乳腺浸润性导管癌HER-2表达状态有高度一致性。IHC可以作为初步筛查乳腺浸润性导管癌HER-2基因状态的首选检测方法,对于IHC检测结果为（++）的标本建议采用FISH法进一步明确HER-2基因扩增状态。     

荧光原位杂交和免疫组织化学方法检测乳腺癌组织中人类表皮生长因子受体2基因状态差异及其特征分析

目的比较荧光原位杂交(fluorescence in situ hybridization,FISH)和免疫组织化学(immunohistochemistry,IHC)检测乳腺癌组织中人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)基因状态差异,分析其相关特征。方法回顾性收集51例中山大学附属第三医院2007年10月至2008年9月间乳腺浸润性导管癌组织标本和相关信息,分别采用IHC和FISH法检测HER-2蛋白表达情况和基因扩增状态,比较两种方法的结果差异,用Fisher精确概率检验分析这种差异的相关因素。结果在51例标本中,FISH检测乳腺癌组织中HER-2基因阴性32例(62.75%,32/51),阳性19例(37.25%,19/51);IHC检测乳腺癌组织中HER-2为(-)和(+)者的FISH检测均为阴性(21例);12例IHC检测HER-2为(++),其中3例FISH检测为阳性,其余9例FISH检测为阴性;18例IHC检测HER-2为(+++)者仍有2例FISH检测结果阴性。月经状态和雌激素受体(ER)表达与IHC检测HER-2阳性病例的FISH阳性结果具有显著联系(P值分别为0.023和0.007),即在IHC检测HER-2阳性[(++)和(+++)]的病例中,绝经前女性较绝经期女性以及ER阴性者较阳性者更可能为FISHHER-2阳性(有HER-2基因扩增)。结论本研究的结果有助于提高IHC判断HER-2基因扩增的准确性。     

HER-2/neu（2+）腔面型乳腺癌的HER-2基因扩增与TopⅡα蛋白及临床特征的关联性分析

目的：分析HER-2基因扩增与腔面型HER-2/neu（2+）乳腺浸润性导管癌的临床病理特征及TopⅡα蛋白的关系。方法运用FISH检测手段对68例雌激素受体（ER）/孕激素受体（PR）阳性的腔面型HER-2/neu（2+）乳腺浸润性导管癌标本进行检测;应用免疫组化法（IHC）对68例标本进行TopⅡα蛋白表达检测。结果 FISH检测结果显示,68例标本中,HER-2基因扩增为13例（19.1%）;HER-2基因扩增在不同年龄、术后病理分期、淋巴结转移数目、Ki-67表达的患者之间差异无统计学意义;HER-2基因扩增病例中,TopⅡαⅠ级6例（46.2%）,Ⅱ级6例（46.2%）,Ⅲ级1例（7.7%）,Ⅳ级0例。TopⅡα蛋白表达情况在有无HER-2基因扩增的乳腺癌间差异无统计学意义（Z=1.353,P=0.176）。结论在HER-2/neu（2+）腔面型乳腺癌中,HER-2基因扩增与年龄、术后病理分期、淋巴结转移数目、Ki-67表达和TopⅡα蛋白表达无关。     

HER2阳性浸润性乳腺癌新辅助治疗反应的预测因子及治疗前后HER2状态变化的评估

背景与目的： 人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阳性浸润性乳腺癌对抗于HER2新辅助治疗的反应显著,然而不同患者的反应并不一致,部分反应较差。本研究旨在探讨HER2阳性乳腺癌新辅助治疗反应的预测因子,并进一步评估新辅助治疗前后HER2状态的不一致性。方法： 收集深圳市人民医院2019—2021年经术前粗针穿刺活检确诊的110例HER2阳性乳腺癌患者,经新辅助治疗后行手术切除。采用免疫组织化学（immunohistochemistry,IHC）及荧光原位杂交（fluorescence in situ hybridization,FISH）检测术前穿刺标本中的HER2表达状态,并评估新辅助治疗后手术切除标本的病理学完全缓解（pathological complete response,pCR）状态及残余肿瘤负荷（residual cancer burden,RCB）分级,评价不同HER2状态对新辅助治疗效果的影响,并进一步比较新辅助治疗前后HER2、雌激素受体（estrogen receptor,ER）及孕激素受体（progesterone receptor,PR）状态的一致性。结果 ：110例乳腺癌患者根据HER2 IHC表达状态分为弥漫3+组（81例）、异质性3+组（20例）和2+且FISH基因扩增（2+FISH+）组（9例）。HER2弥漫3+组pCR率为54.3%,明显高于异质性3+组（5.0%）和2+FISH+组（11.1%）,差异有统计学意义（P<0.05）,而异质性3+组和2+FISH+组的RCB分级更高。多因素分析显示,HER2弥漫3+是pCR的独立预测因子。7例（11.9%）HER2阳性乳腺癌患者在新辅助治疗后HER2转为阴性,大多数（85.7%）为异质性3+组和2+FISH+组病例。结论： HER2异质性会影响HER2阳性乳腺癌的新辅助治疗反应,评价穿刺活检标本中HER2 IHC异质性,并对新辅助治疗后残留癌灶HER2、ER和PR状态重新评估,有利于指导下一步治疗。新型抗体药物偶联物（antibody-drug conjugate,ADC）的出现有望为HER2异质性阳性乳腺癌患者带来生存获益。     

乳腺癌组织与转移淋巴结HER-2基因表达及检测方法的比较

目的 探讨乳腺癌组织与转移淋巴结中人表皮生长因子受体（human epidermal growth factor receptor-2, HER-2）基因表达的情况,对比荧光原位杂交法（Fluorescence in situ hybridization, FISH) 与免疫组织化学法（Immunohistochemistry,IHC）两种检测方法。方法 选取187例乳腺癌组织和76例转移淋巴结石蜡包埋标本,采用FISH和IHC方法检测HER-2基因表达,分析HER-2过表达与各临床病理因素的关系以及两种检测方法的差异,比较原发灶与转移灶HER-2表达的状况。结果 187例乳腺癌组织中,FISH检测显示HER-2阳性43例,阴性144例。IHC评分+++者22例、评分++者40例、评分-/+者125例。IHC评分+++者中,FISH阳性率为90.9%（20/22）;评分++者中,FISH阳性率为52.5%（21/40）;评分0/+者中,FISH阳性率为1.6%（2/125）。两种方法相比差异有统计学意义（P<0.001）。临床病理因素分析示HER-2基因扩增与淋巴结转移呈正相关 (P<0.05)。乳腺癌原发灶与其配对转移淋巴结相比,HER-2表达的不一致性为11.8%(9/76)。结论 FISH较之IHC检测HER-2表达准确性更高,尤适用于对IHC ++的患者判断HER-2的表达。乳腺癌原发灶与转移灶之间HER-2的表达存在一定的不一致性。     

IHC、FISH与CISH检测乳腺癌Her-2基因状态的对比研究

目的 比较免疫组织化学法(IHC)、荧光原位杂交法(FISH)与显色原位杂交法(CISH)检测乳腺癌HER2基因状态的一致性,探讨FISH法与CISH法榆测乳腺癌HER2基因状态的临床意义.方法 对64例乳腺浸润性导管癌石蜡标本分别应用IHC法、CISH法与FISH法检测HER2蛋白、HER2基因状态及17号染色体多体的发生率.结果 HER2蛋白表达(+++)组,IHC与CISH、FISH法检测HER2基因扩增阳性的符合率均为100%;HER2蛋白表达(++)组,IHC与CISH、FISH法检测的符合率分别为95.83%与91.67%;HER2蛋白表达(+/-)组,IHC与CISH、FISH法检测的符合率亦均为100%.FISH法与CISH法的检测结果1例存在差异,FISH法与CISH法检测HER2基凶状态总的符合率为98.41%.17号染色体多体的发生率在IHC(+++、++、+/-)三组中分别为45.16%、45.83%和11.11%,其总的发生率为40.62%.结论 IHC法柃测HER2蛋白仅作为初筛方法;FISH法与CISH法检测HER2基因状态存在较高程度的符合率,CISH法可作为一种更加方便可行的方法检测HER2基凶状态;在疑有17号染色体多体干扰时,应进一步行FISH法检测.     

色素原位杂交法和免疫组织化学法检测乳腺癌HER-2基因扩增及蛋白表达

目的:对照色素原位杂交法(chromogenic in situ hybridization,CISH)和免疫组织化学法(immuno-histochemistry,IHC)检测乳腺癌组织中人表皮生长因子受体(human epidermal growth factor receptor-2,HER-2)基因扩增及其蛋白表达的状况.方法:采用CISH技术检测145例乳腺癌组织中HER-2的基因扩增情况,其中14例标本经过荧光原位杂交(fluorescence in si-tu hybridization,FISH)检测,随后分别用FISH和IHC方法检测的HER-2基因扩增及蛋白表达状况与之进行回顾性对照,并按照病理分级、淋巴结状态、绝经与否和雌激素受体(estrogen receptor,ER)/孕激素受体(progesterone receptor,PR)表达情况进行分层,分析HER-2表达与乳腺癌各高危因素之间的关系.结果:CISH检测发现,HER-2无扩增71例(50.0%),低扩增11例(7.6%),高扩增63例(43.4%).14例FISH与CISH检测结果比较,符合率为100.0%.145例IHC与CISH检测结果的符合率为84.8%(P<0.05).在IHC检测积分为0/ 以及 的病例中,HER-2基因扩增与蛋白表达情况基本一致,其符合率均在90%以上;而在IHC检测积分为 的标本中,HER-2基因扩增率仅为61.1%.CISH及IHC检测均显示ER/PR表达情况与HER-2阳性呈负相关,ER和PR均为阴性患者的HER-2基因扩增率和蛋白表达率明显高于ER/PR阳性的患者(CISH:68.3%vs 38.8%,P<0.01;IHC:71.7%vs 48.2%,P<0.01).HER-2状态与乳腺癌病理分级、腋淋巴结转移以及绝经与否无关(P>0.05).结论:CISH技术检测HER-2操作简便,准确性高,可以代替FISH技术,对IHC评分为 的病例应进一步确认HER-2状态.HER-2除了与ER/PR表达相关外,与其他乳腺癌高危因素无关,可作为独立指标进行检测.     

荧光原位杂交检测乳腺癌HER2（++）扩增状态及其与临床病理的相关性

目的 使用荧光原位杂交（fluorescence in situ hybridization, FISH）检测HER2基因扩增情况,并探讨影响HER2基因扩增的因素及其与临床病理特征的关系。方法 收集新疆医科大学附属肿瘤医院2013年l月至2015年12月间IHC检测HER2（++）的乳腺癌病例325份,均采用IHC和FISH两种方法分别检测所有患者的石蜡标本HER2表达和扩增情况,并分析HER2扩增状态与患者各临床病理特征的关系。结果 全组患者经IHC检测HER2表达均为（++）,FISH检测HER2扩增率为12.9%（42/325）,对12项临床和病理指标进行单因素分析显示：HER2扩增状态与激素状态、肿瘤直径、P53显著相关（P<0.05）,而与ki67表达、组织学分级、肿瘤个数等因素均无关（P>0.05）。结论 雌孕激素表达均阴性、肿瘤直径>2 cm、P53表达阳性是预测FISH检测IHC HER2（++）扩增的独立因素。     

Status of HER2 amplification, polysomy 17 and histopathological features of 425 Pakistani breast cancer patients

HER2 gene amplification in invasive breast cancer is a robust predictive marker for response to transtuzumab therapy. This study was undertaken to measure concordance between immunohistochemistry (IHC) and FISH for HER2 gene amplification in invasive breast tumors, as well as the presence of polysomy 17 and possible correlation with demographics and histopathological variables, including ER and PR positivity. A total of 425 cases of infiltrating carcinoma of breast (99% IDC-NOS) were studied. HER2 over expression was tested by IHC and FISH methods. Association between IHC and FISH in both subsets was calculated by amplification ratio including polysomy 17. Out of 425 specimens, 128 (30%) were positive for HER2 amplification by FISH test, whereas only 78 (24%) tumors with 2+ expression showed amplification. In contrast, 39 (74%) demonstrated 3+ IHC score and HER2 gene amplification. The histological variables including tumor size, tumor type, and lymph node involvement did not influence the outcome of FISH analysis. The ER and PR status showed significantly greater positivity in patients negative for HER2 amplification. Polysomy 17 was detected in 23.7% patients and was positively associated with ER and PR expression (P= <0.05). Our study showed a concordance of 24% between 2+ IHC and FISH amplification, while in 3+ IHC cases the concordance was 74%. Significant links of HER2 amplification was seen with ER andPR negativity and higher tumor grade. In addition, non-significant correlations were noted with other variables like tumor type, size and lymph node status.     

Immunohistochemistry Subtypes (ER/PR/HER) of Breast Cancer: Where Do We Stand in the West of Saudi Arabia?

In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer deathin the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate,these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. Thepresent report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal andlobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors(age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety ninecases of breast tumors were recruited from the pathology department archive of King Abdulaziz UniversityHospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductalcarcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59(62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order.Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal andlobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 inSaudi female is different from that of Tunisian and Jordanian female populations and closer to the expressionpattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found twoIHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reportedin other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation amongArabic female populations.     

Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort

Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22–46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.     

HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues

To analyze HER2 amplification in a large cohort of diagnostic breast cancer specimens, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on the same specimens with use of Food and Drug Administration&approved products. Procedures were standardized following the manufacturers' recommendations. Of 116,736 IHC specimens, 20% were positive for HER2. In 16,092 FISH specimens, 22.7% showed HER2 amplification. In the subset of 6556 tissues analyzed with IHC and FISH, however, 59% were positive on IHC and 23.6% were amplified on FISH. The increased frequency of positive test results is skewed by more frequent reflex FISH testing. In general, expression and amplification trended together, with the least amplification (4.1%) seen in IHC-negative cases, 7.4% amplification seen in IHC 1+ cases, 23.3% amplification seen in IHC 2+ cases, and 91.7% amplification seen in IHC 3+ cases. When FISH amplification ratios were stratified, the low FISH ratios (2.0-2.2) were most frequently seen in specimens with negative IHC results, high ratios (>5.0) were seen in IHC 3+ specimens, and intermediate levels of amplification were similar for all levels of IHC. The effect of changing the cutoff point was analyzed: removing cases with a ratio of exactly 2.0 decreased the FISH positivity rate to 22.2% in the combined IHC and FISH cohort. Sequentially moving the cutoff point to 2.2 and 2.5 affected cases at all IHC expression levels. Each change removed approximately 2% from the apparent positivity. This large database provides the distribution frequency of HER2 protein expression and gene amplification in invasive ductal and lobular breast cancer. The relationship between level of HER2 amplification and clinical outcome will require reanalysis of pivotal trial data.     

Prognostic utility of fluorescence in situ hybridization for determining HER2 gene amplification in breast cancer

An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P<0.0001). However, some mismatching was evident: 3 cases, negative for the HER2 gene, showed a HER2 protein expression score of 3+ and 2 cases, positive for HER2 gene amplification, had HER2 protein expression scores of 0 and 1+ (negative), respectively. ER and PR were expressed in 41 (66%) and 46 (74%) cancers, respectively. No correlation was observed between the HER2 gene amplification and any of the clinicopathological parameters examined, including age, histopathological type, TNM stage, tumor size, lymph node status, relapse and expression of PR. We observed three patterns among the 6 deceased cases: i) triple negativity for HER2, ER and PR, ii) positivity for HER2 gene amplification with a mismatching HER2 protein expression, and iii) positivity for the HER2 gene amplification with a matching HER2 protein expression score of 2+ or 3+. The triple negative cases and HER2 gene amplification positive cases with a mismatching HER2 protein expression had a poor outcome. These results suggest that in breast cancer, the detection of HER2 gene amplification by FISH is desirable compared with the HER2 protein expression determined by IHC. Moreover, triple negativity for HER2, ER and PR is a potentially very important prognostic marker.     

Histological grade,p53, HER2 and hormone receptor status of synchronous bilateral breast carcinoma

BACKGROUND AND OBJECTIVES: Histological grade and tumor biology remain important predictors of the clinical behavior of breast carcinomas. We analyzed the clinicopathological characteristics and tumor biology with regard to histological grade (HG), p53, HER2 and hormone receptor status to address this question. PATIENTS AND METHODS: A consecutive series of 74 female synchronous bilateral breast carcinoma patients treated at the National Cancer Center Hospital were the primary source of these retrospective data. Clinicopathological background factors, histological grade and immunohistochemical staining for p53, HER2 and hormone receptor status, were analyzed. RESULTS: Of 148 synchronous bilateral tumors, 102 were invasive ductal carcinoma (IDC). The others included 24 pure or predominant ductal carcinoma in situ (DCIS), 5 spindle cell carcinomas, 16 invasive lobular carcinomas and 1 squamous cell carcinoma. 128 cases (128/148: 89%) were HG 1 (72/148: 49%) or HG 2 (56/148: 38%). The positivity rates for p53, HER2, estrogen receptor (ER) and progesterone receptor (PR) were 9%(14/148), 18%(26/148), 64%(95/148) and 64%(95/148), respectively. CONCLUSION: Our findings indicate that synchronous bilateral breast carcinomas showed a higher frequency of invasive lobular carcinoma, lower HG and higher rate of hormone receptor positivity than unilateral breast carcinomas.     

Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan

The management and prognosis of breast cancer nowadays require the evaluation of Estrogen (ER), Progesterone Receptors (PR) and HER2/neu. Ethnic variation in the expression of these receptors is well documented. The aim of this study is to determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast cancer of ductal and lobular types. A retrospective analysis was performed on 267 cases of breast cancer referred for treatment at King Hussein Cancer Center, Jordan between the period of June 2003 and June 2004. Standard immune stains were used for evaluation of hormone receptors and HER2/neu. In addition, evaluation of HER2/neu was done by FISH in selected cases. Of these 267 cases, 240 (89.9%) were ductal carcinomas of various histological grades, 122 (50.8%) of which were ER-positive, 138 (57.5%) PRpositive and 42 (17.5%) HER2/neu-positive. Twentytwo (8.2%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive, 20 (90.9%) PRpositive and 3 (13.6%) HER2/neu-positive. Five (1.9%) of the total cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive, 3 (60%) PR-positive and none were positive for HER2/neu. The prevalence of hormone receptor positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans).     

Association between GSTP1 Genotypes and Hormone Receptor Phenotype in Invasive Ductal Carcinomas of Breast

Eighty six cases of invasive ductal breast carcinomas were utilized to investigate GSTP1 polymorphisms incertain immunohistochemistry (IHC) subtypes of breast cancer with respect to ER, PR and HER2 expression.The frequency of wild allele homozygote, heterozygote and variant allele homozygote genotypes were 46.5%,52.3% and 1.16% respectively; Whereas 54.3% of the control subjects were GSTP1 wild type allele homozygous,40.0% were heterozygous and 5.71% mutant allele homozygous. There was dramatic inverted relation betweenpositive IHC ER staining and increasing grade of tumors in general (100%, 88.6%, 40.4%) and especially amongtumors with heterozygote genotype of GSTP1 (70%, 35.4%, 22.7). There was increase in positive IHC HER2staining consistent with higher grades in general (20%, 29.6%, 50.0%), especially among tumors with GSTP1wild allele homozygote genotype (5.0%, 9.1%, 31.8%). A remarkable reverse relation was also observed betweenthe fraction of IHC hormone receptor phenotype ER+/PR+/ HER2- and increased grade of tumors (60.0%,45.5%, and 27.3%) especially among tumors with GSTP1 heterozygote genotype, and a similar link was notedregarding ER+/PR-/ HER2- and tumor grade. There was increase in frequency of ER-/PR-/ HER2- (0.0%, 6.8%,and 18.2%) and ER-/PR-/ HER2+ (0.0%, 4.54%, and 40.9%) consistent with the higher grades of tumors ingeneral and especially GSTP1 heterozygote genotype tumors. As a conclusion, there is no correlation betweenGSTP1 polymorphism and increased risk of breast cancer i.e. the mutant allele is randomly distributed in cancerand control cases. However, there is a link between GSTP1 genotypes and hormone receptor expression statusand certain phenotypes of breast cancer, which may have clinical importance.     

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as 10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3 by IHC. For HER2 (2), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor sizealso Ki-6720% as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index 20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-6720% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.     

A Retrospective Hospital-Based Study of HMGCR Expression in HER2 IHC 2+ and 3+ Breast Cancer

Objective: The role of HMG-CoA reductase (HMGCR) in relation to prognostic and treatment predictive information of HER2 positive breast cancer has been newly explored. In this study, we aimed to determine the expression of HMGCR in HER2 immunohistochemistry (IHC) scores of 2+ and 3+ breast cancer and to correlate with the patients’ outcomes.Methodology: Using a cross-sectional design, invasive breast carcinoma of no special type (NST) and HER2 IHC scores of 2+ and 3+ cases were selected over a 50-month period in Hospital Sultanah Bahiyah (HSB), Alor Setar. IHC staining for HMGCR was performed on paraffin-embedded tissues at the Pathology Laboratory, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian using the standard staining procedure. The results were correlated with the patient’s demographic and clinicopathological data. Results: A total of 59 cases of HER2 IHC 2+ and 3+ invasive breast carcinoma were identified. The cases were predominant in young Malay women with tumours smaller than 50mm, higher grade and positive for lymphovascular invasion, axillary lymph nodes involvement and ER/PR expressions. HMGCR was positively expressed in HER2 IHC 2+ and 3+ breast cancer cases, which the staining intensities varied from weak, moderate to strong. Majority of the cases were scored 1+ for HMGCR expression. A low-positive HMGCR was more likely to be associated with less favourable outcomes of patients with HER2 IHC 2+ and 3+. However, the associations were statistically not significant. Conclusion: A study in a larger cohort of tumour samples is needed to further validate HMGCR expression as a potential prognostic biomarker for HER2 positive breast cancer. It is also suggested that all the HER2 IHC 2+ and 3+ cases need to be gene amplified using FISH analysis.