新辅助化疗后乳腺癌的临床病理学改变

目的 旨在观察局部进展期乳腺癌新辅助化疗的临床病理学改变。方法 局部进展期乳腺癌40例术前用粗针穿刺获组织学检查证实为乳腺癌，并作免疫组化进行ER、PR、cerb-B2、p53、Ps2、nm23、CathD等项目检测，新辅助化疗采用TA化疗方案，3周为一个周期，完成2-6周期不等进行临床评价疗效。对术后标本进行HE、免疫组织化学染色观察。结果总有效率(RR)为90．0％(36／40)，13例(32．5％)临床完全缓解(cCR)，23例(57．5％)部分缓解(PR)，4例(10．0％)无变化(NC)，无进展病例。其中9例(22．5％)病理完全缓解(pCR)。行保乳手术10例(10140)。与术前病理检验标本比较，乳腺癌化疗后出现瘤体缩小变软、甚至消失，肿瘤细胞退变坏死、间质水肿、玻璃样变性、血管周围炎症细胞浸润及纤维化等改变；相应病例腋窝淋巴结转移灶亦有上述改变，而且淋巴结无论有无转移均可见结构改变，淋巴细胞松散，正常滤泡结构消失，甚至于出现正常淋巴结不见的充血现象，有大量噬细胞反应。免疫组织化学未见P53、cerb-B2、CathD蛋白阳性表达变化，ER、PR表达无显著差异。结论 TA新辅助化疗对多数乳腺癌的原发灶及腋窝淋巴结转移灶均不同程度变性坏死，增加了保乳手术机会，同时在抑制乳腺癌微转移灶、降低复发及转移等方面具有重要临床意义。     

雌、孕激素受体表达与宫腔粘连分离术后雌孕激素治疗疗效的相关性研究

目的:研究宫腔粘连(IUA)患者子宫内膜组织中雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)的表达,探讨其与术后雌孕激素治疗疗效的关系。方法:采用免疫组化法检测55例中重度IUA患者子宫内膜组织的ER、PR表达;患者均行宫腔镜下IUA分离术,术后给予雌孕激素周期治疗。随访患者的月经改善情况,结合宫腔镜复查结果,分析PR、ER受体与预后的相关性。结果:ER、PR在腺体及间质中的表达均无显著差异(P=0.727,P=0.453);PR低表达组、高表达组患者术后雌孕激素治疗的有效率分别为63.64%和54.55%,两组比较无显著差异(P=0.503);ER低表达组、高表达组患者术后雌孕激素治疗的有效率分别为33.33%和70.27%,两组比较差异显著(P=0.018)。结论:患者子宫内膜PR的表达不能预测预后;ER表达水平与疗效呈正相关,其可能成为IUA术后雌孕激素治疗疗效的预测指标。     

表阿霉素联合紫杉醇的新辅助化疗治疗乳腺癌的临床观察

目的 评价表阿霉素(EPI)联合紫杉醇(TAX)进行新辅助化学治疗乳腺癌的疗效及不良反应。方法用EPI联合TAX治疗Ⅱ、Ⅲ期乳腺癌26例,其中EPI 60 mg/m2,第1天静注,TAX 150 mg/m2,第2天持续3 h静滴,4周为1个疗程。所有患者化疗2个周期后行乳腺癌改良根治术,术后继续以原方案化疗4~6个周期。化疗前给予地塞米松、蒽丹西酮、苯海拉明和西米替丁预防胃肠道不良反应及过敏反应。结果乳腺癌有效率(RR)81％(21/26),其中Ⅱ期乳腺癌达94％(15,16),Ⅲ期为60％(6,10)。无病理完全缓解病例,1例(4％)临床完全缓解(cCR),20例(77％)部分缓解(PR),5例(19％)无变化(NC),无进展病例。腋窝肿大淋巴结中62％(16/26)新辅助化疗后不能触及,其中N1达75％(15/20),N2为17％(1/6)。主要不良反应为白细胞下降、关节肌肉痛、神经毒性、胃肠道反应、脱发和面色潮红,均可耐受。结论EPI联合TAX进行新辅助化疗是一种安全、有效、可行的方法,能明显缩小乳腺癌的原发肿瘤及腋窝淋巴结转移灶。     

米非司酮对子宫肌瘤组织中雌孕激素受体和表上生长因子受体的影响

目的：探讨米非司酮对子宫肌瘤组织内雌、孕激素受体和表皮生长因子受体的影响。方法：44例子宫肌瘤患者作全子宫切除或子宫肌瘤挖出术，其中米非司酮组16例，术前予米非司酮25mg，每日2次，连用3个月；对照组28例。采用免疫组化法测定子宫肌瘤及子宫平滑肌内雌、孕激素受体含量，用流式细胞仪测定EGFR水平。结果：米非司酮组子宫肌瘤及子宫平滑肌内PR较对照组显著下降（P＜0．01），ER无显著差异；米非司酮组子宫肌瘤及子宫平滑肌EGF－R水平显著低于对照组（P＜0．01）。结论：子宫肌瘤内EGF－R减少是米非司酮治疗后子宫肌瘤缩小的重要机制，这一作用可能与米非司酮阻断孕酮与PR的结合有关。     

卵巢肿瘤组织雌、孕激素受体测定

用葡聚糖—活性炭吸附法测定14例正常卵巢、14例良性卵巢肿瘤和44例卵巢恶性肿瘤的胞浆雌、孕激素受体(EcR、PcR)和胞核孕激素受体(PnR)。结果显示恶性卵巢肿瘤的EcR中位数、EcR阳性率及EcR、PcR双阳性率均高于其他两组,EcR、PcR双阴性率低于其他两组。PnR的测定结果与PcR的结果一致。高分化卵巢癌的EcR及PcR含量高于低分化肿瘤,作者认为一部分卵巢肿瘤存在ER、PR,提供了内分泌治疗奏效之可能,应用受体测定可防止激素治疗的盲目性。     

人子宫平滑肌肿瘤的雌、孕激素受体和p~(53)蛋白表达

目的：探讨子宫平滑肌瘤与雌、孕激素受体的关系；了解ｐ５３蛋白在不同组织学类型肌瘤细胞内的表达情况。方法：直接荧光组织化学法和免疫组化法。结果：子宫肌瘤雌、孕激素受体阳性率为６５．５２％，高于子宫肌壁的雌、孕激素受体３６．３６％的阳性率。两组差异有显著性（Ｐ＜０．０５）。６０例子宫平滑肌瘤ｐ５３蛋白总阳性表达率为１８．８３％，良性平滑肌瘤组、富细胞型及子宫肉瘤组ｐ５３蛋白阳性率分别为１３．３３％、１５％和４０％。肉瘤组ｐ５３蛋白阳性率明显高于良性肌瘤组，但差异无显著性。结论：雌、孕激素对子宫平滑肌瘤的发生均有一定作用。人子宫平滑肌瘤ｐ５３蛋白阳性表达率低于女性生殖道上皮源性肿瘤，而与人纤维源性肿瘤的ｐ５３蛋白阳性表达率接近。     

乳腺癌中survivin表达及变化与紫杉醇疗效的相关性

目的探讨乳腺癌中survivin的表达水平及其在化疗前后表达水平的变化与紫杉醇作用效果之间的相关性。方法选取60例接受新辅助化疗的乳腺癌，用免疫组织化学的方法分别检测化疗前后survivin的表达情况，并评价化疗的疗效。结果Survivn阴性和强阳性组相比及弱阳性组与强阳性组相比，前者的化疗效果优于后者，差异有统计学意义。获得临床稳定（SD）的患者与获得临床部分缓解（PR）、临床完全缓解（cCR）的患者相比，前者化疗后survivin上调的比例要明显高于后者，两者之间存在统计学差异。结论survivin的过表达可能与紫杉醇的耐药性相关。     

米非司酮对子宫肌瘤组织中雌孕激素受体和表皮生长因子受体的影响

目的　探讨米非司酮对子宫肌瘤组织内雌、孕激素受体和表皮生长因子受体的影响。方法　 44例子宫肌瘤患者作全子宫切除或子宫肌瘤挖出术 ,其中米非司酮组 16例 ,术前予米非司酮 2 5mg ,每日 2次 ,连用 3个月 ;对照组 2 8例。采用免疫组化法测定子宫肌瘤及子宫平滑肌内雌、孕激素受体含量 ,用流式细胞仪测定EGF -R水平。结果　米非司酮组子宫肌瘤及子宫平滑肌内PR较对照组显著下降 (P <0 0 1) ,ER无显著差异 ;米非司酮组子宫肌瘤及子宫平滑肌EGF -R水平显著低于对照组 (P <0 0 1)。结论　子宫肌瘤内EGF -R减少是米非司酮治疗后子宫肌瘤缩小的重要机制 ,这一作用可能与米非司酮阻断孕酮与PR的结合有关。     

子宫内膜癌p53蛋白过度表达与性激素受体阳性的关系

目的：研究子宫内膜癌ｐ５３蛋白过度表达与性激素受体阳性的关系。方法：收集４５例子宫内膜癌手术标本，采用多种ＰＡＰ免疫组化方法进行检测。结果：４５例宫内膜癌中１４例（３１．１％）ｐ５３蛋白过度表达，其中１１例雌、孕激素受体阴性，而在ｐ５３阴性的３１例中２７例雌、孕激素受体阳性。在子宫内膜癌中ｐ５３蛋白过度表达与雌、孕激素受体呈负相关（Ｐ＜０．０１）。结论：部分子宫内膜癌的发生可能与雌激素受体无关，而与ｐ５３蛋白过度表达有关。     

三苯氧胺对人乳腺癌的雌激素受体的上调作用

东莞氧胺(TMX)为一非固醇类雌激素拮抗剂,广泛用于晚期和复发乳腺癌。TMX使约60％雌激素受体(ER)阳性和10％ER阴性的乳腺癌肿缩小。一些临床试验表明,对ER阳性的绝经后乳腺癌患者TMX可作为一有效辅助治疗。目前尚未阐明在体内TMX治疗对人乳腺癌ER和孕激素受体(PR)水平的影响。在本研究中,作者试图从同一乳腺癌中获得系列细针穿刺吸引(FNA)标本,用酶联免疫法(EIA)检测TMX对人乳腺癌ER水平的影响及对PR的影响。     

Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, adriamycin, and cyclophoshamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures

BACKGROUND: Neoadjuvant administration of chemotherapy provides a unique opportunity to monitor response to treatment in breast cancer and assesses response exactly. Global gene expression profiling by microarrays has been used as a valuable tool for the identification of prognostic and predictive marker genes. Even though this technology is now wide spread and relatively standardized, there are only few data available which compare established parameters with expression values to determine reliability of this method. Therefore we analyzed gene expression data of pretreatment biopsies of breast cancer patients and compared them with the results of the immunohistochemical receptor expression for ER/ PR and Her-2, as well as FISH testing for HER-2 amplification. We analyzed the change of expression of these markers before and after neoadjuvant chemotherapy. Furthermore we evaluated the predictive significance of prognostic gene signatures as described by Sorlie, van't Veer and Ahr for response to neoadjuvant chemotherapy. METHODS: Pretherapeutic core biopsies were obtained from 70 patients undergoing neoadjuvant TAC chemotherapy within the GEPARTRIO-trial. Samples were characterized according to standard pathology including ER, PR and HER2 IHC and amount of cancer cells. Only biopsies with more than 80 % tumor cells were considered for further examination. RNA was isolated and expression profiling performed using Affymetrix Hg U133 Arrays (22 500 genes). GeneData's Expressionist software was used for bioinformatic analyses. RESULTS: More than two thirds of the biopsies yielded sufficient amounts (> 5 microg) of RNA for expression profiling and high quality data were obtained for 50 samples. Unsupervised clustering broadly revealed a correlation with hormone receptor status. When ER-alpha, PR and HER2 as analyzed by immunohistochemistry were compared to the corresponding mRNA data from gene chips more than 90 % concordance was observed. We could observe a switch of receptor expression for ER, PR or HER-2 from positive to negative and vice versa in 16/35 cases (45.7 %) and 5/22 cases (22.7 %) respectively. The prognostic marker sets of Sorlie, van't Veer and Ahr could not discriminate responders from non-responders in our patient group. CONCLUSIONS: Our results demonstrate that reliable expression profiles can be achieved by using limited amounts of tissue obtained during neoadjuvant chemotherapy. Microarray data capture conventional prognostic markers but might contain additional informative gene sets correlated with treatment outcome. Prognostic marker sets are not suitable to predict tumor response in the neoadjuvant setting, suggesting the necessity of class prediction methods to identify marker sets predictive for the type of therapy used.     

Steroid hormone receptors in carcinoma of the cervix: lack of response to an antiestrogen

Levels of estrogen (ER) and progesterone (PR) receptors were measured in 81 patients with primary cervical cancer. In 10 patients, receptor levels were evaluated before and after a short course of tamoxifen treatment. Fifty-six percent of cervical tumors contained ER, and 58%, PR. Receptor level and expression were not related to any clinical and histological characteristic. Moreover, both survival time and response to neoadjuvant chemotherapy did not correlate with the presence of ER and PR. Tamoxifen treatment did not influence ER and PR levels. Our results suggest that steroid hormone receptors are of little value in the management of cervical cancer, and that in this neoplasia, ER is probably not functional.     

May progesterone receptor membrane component 1 (PGRMC1) predict the risk of breast cancer?

Objective: Our and other studies have pointed on an important role of progesterone receptor membrane component 1 (PGRMC1) in development of breast cancer, especially in hormone therapy. To investigate if PGRMC1 could be used to predict the risk for getting breast cancer, we assessed in tissues of patients with primary invasive breast cancer, if the expression of PGRMC1 may be associated with the expression of estrogen receptor alpha (ERα), progesterone receptor (PR), and ki67.

Methods: Samples from 109 patients with breast cancer between the years 2008 and 2014 were obtained with the patients’ consent. Each sample was evaluated for the ERα, PR, Ki67, and PGRMC1 expression by immunohistochemistry using serial sections from the ame paraffin block comparing malignant tissue to benign tissue.

Results: Expression of PGRMC1 is increased in tumor area compared with non-cancerous tissue and positively correlates with ERα expression (OR?=?1.42 95%CI 1.06–1.91, p?=?0.02). No association was obtained between expression of PGRMC1 and PR or Ki67.

Conclusion: It can be suggested that women with breast epithelium highly expressing PGRMC1 and in interaction with ERα may have an increased risk to develop breast cancer, especially when treated with hormone therapy.     

Randomized study of preoperative chemotherapy versus primary surgery for stage IB cervical cancer

AIM: To determine the most effective treatment and long-term outcome of patients with stage IB carcinoma of the cervix. METHODS: From January 1999 to December 2001, 106 women with cervical cancer stage IB received neoadjuvant chemotherapy (n = 52) or primary surgery (n = 54). These were randomly assigned. Clinical effects and pathological changes were simultaneously recorded. RESULTS: The overall clinical response rate was 84.6% and included a complete response (CR) in four patients (7.7%), partial response (PR) in 40 patients (76.9%), and stable disease (SD) in the remaining eight patients (15.4%). Surgery revealed positive nodes in 9.6% neoadjuvant chemotherapy group patients and in 29.6% primary surgery group patients (P = 0.014). Similar results occurred with vascular space involvement: 27.8% in the primary surgery group compared to 9.6% in the neoadjuvant chemotherapy group (P = 0.024). However, parametrial infiltration was found in 7.4% of the patients in the primary surgery group, while only 3.8% showed it in the neoadjuvant chemotherapy group (P = 0.679). The overall 5-year survival rate was significantly higher for all patients who received neoadjuvant chemotherapy (84.6%) than for the control group (75.9%) (P = 0.0112). The median survival time in patients with complete response and partial response to chemotherapy (83.3 months) was significantly higher than that of patients with stable disease to chemotherapy (55.2 months) (P = 0.0049). 27.3% of patients developed recurrent disease within 5 years of the primary treatment. The women with recurrence included partial response in six patients (60.0%), and stable disease in four patients (40.0%). For the other patients there was partial response and complete response in 38 patients (90.5%), and stable disease in the remaining four patients (9.5%) (P = 0.035). CONCLUSION: Neoadjuvant chemotherapy can effectively eliminate the pathological risk factors and improve long-term survival in patients with locally advanced cervical cancer.     

Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable,advanced-stage ovarian cancer

OBJECTIVE: The aim of this review is to report our experience and the feasibility of neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer. METHODS: Forty-five patients with primarily unresectable advanced-stage epithelial ovarian cancer were treated in our center between 1995 and 2002 by platinum-based neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Their files were reviewed retrospectively. RESULTS: At the end of neoadjuvant chemotherapy, according to RECIST criteria, 1 patient (2.2%) had achieved a clinical complete response (CR), 33 (73.4%) a partial response (PR), and 8 (17.8%) had stable disease (SD). Only 3 (6.6%) patients showed disease progression (PD). Surgery was performed in patients with objective response or SD after a median number of 4 courses (range: 2-6) of induction chemotherapy. A complete macroscopic debulking was achieved in 24 (53.3%) out of 39 patients in whom cytoreductive surgery was performed. For the entire group, median overall survival was 29 months. Survival was significantly improved in patients with optimal debulking compared to patients with persistent tumor after surgery: 41 months versus 23 months (P = 0.0062). Median survival for patients responding to neoadjuvant chemotherapy (CR and PR) was 44 months compared to 27 months for patients with SD or PD after initial chemotherapy (P = 0.01). Neither treatment-related deaths nor significant toxicities were observed. CONCLUSION: Neoadjuvant chemotherapy followed by optimal debulking may be a safe and valuable treatment alternative in patients with primarily unresectable advanced-stage bulky ovarian cancer. Patients with an objective response to chemotherapy or absence of macroscopic residual tumor after surgery have a better outcome. This approach is currently being tested in large, prospective randomized clinical trials.     

Prognostic molecular markers and neoadjuvant therapy response in anthracycline-treated breast cancer patients

Background

Identifying biomarkers that can predict the prognosis and treatment response is helpful for individualizing breast cancer (BC) therapy. A neoadjuvant treatment setting is ideal for testing biomarkers capable of predicting the treatment response. This study analyzed the value of immunohistochemical biomarkers for predicting pathological complete response (pCR) and prognosis in a group of BC patients receiving standardized treatment.

Patients and methods

A total of 100 BC patients were treated with neoadjuvant chemotherapy (four cycles of epirubicin and cyclophosphamide) between 2000 and 2005. Formalin-fixed and paraffin-embedded core biopsies were taken before chemotherapy for immunohistochemical staining of ER, PgR, HER2, Bcl-2, p53, cyclin D1, CK5/6, CK8, CK18, and TOP2A. Patient and tumor characteristics and biomarker scores were used to predict pCR and prognosis, using logistic regression and Cox proportional hazard models.

Results

pCR was achieved in 11 patients and was predicted by the established marker Ki-67. In addition, CK5/6 and CK18 improved the prediction model and were associated with lower pCR rates. For the prognosis, only the established markers nodal status, Ki-67, and PgR predicted overall survival and nodal status; Ki-67 and PgR predicted distant disease-free survival.

Conclusions

In this small retrospective study, CK5/6 and CK18 appeared to improve prediction of pCR in addition to the established markers. CK5/6 may indicate a tumor type resembling a basal phenotype that is more resistant to anthracycline-based therapy, and CK18 may indicate a luminal subtype that is more resistant to chemotherapy. However, these results need to be replicated in larger studies.     

局部晚期子宫颈癌新辅助化疗价值的评估

目的 探讨局部晚期宫颈癌新辅助化疗的疗效及影响近期疗效的相关因素,以及对患者长期生存的影响。方法 收集行新辅助化疗的Ⅰb2—Ⅱb期局部晚期宫颈癌患者64例,分析其化疗后的近期疗效及长期生存率,采用多元线性回归法分析影响化疗近期疗效的相关因素。结果 新辅助化疗的近期总有效率为80％（51／64）。化疗患者的近期疗效与病理类型有关,鳞癌患者的有效率（82％）明显高于腺癌（6／9,P〈0．05）;而与其他因素无关（P〉0．05）。化疗有效者手术后盆腔淋巴结阳性率为8％（4／51）,宫旁血管癌栓阳性率为2％（1／51）,均明显低于化疗无效者（分别为3／6、2／6;P〈0．05）。新辅助化疗后患者的总5年生存率为89％,其中化疗有效者5年生存率为100％,明显高于化疗无效者的46％（P〈0.05）。新辅助化疗有效者3、5年无瘤生存率分别为95％、83％,化疗无效者分别为33％、0,两者分别比较,差异均有统计学意义（P〈0．05）。结论 局部晚期宫颈癌新辅助化疗的近期疗效与病理类型有关,对化疗有效者应选择手术,可提高长期生存率。