15-PGDH expression as a predictive factor response to neoadjuvant chemotherapy in advanced gastric cancer

Given the various clinical and pathologic responses to neoadjuvant chemotherapy (NACT) in gastric cancer (GC), potential biomarkers that reflecting the efficacy of NACT on GC should be investigated. The aim of this study was to investigate the 15-PGDH expression response to NACT in GC patients and its relationship with prognosis of GC. Immunohistochemical method was used to assess the level of 15-PGDH expression in 56 GC patients who received NACT before surgery and 46 patients who underwent surgical treatment without NACT as well as their corresponding adjacent non-neoplastic tissues. We found that there was no correlation of 15-PGDH expression between non-cancerous gastric tissues and GC tissues (P=0.519), while 15-PGDH expression level in NACT group was higher than that in nNACT group (P=0.015). In patients with NACT, the higher level of 15-PGDH expression was significantly associated with well-moderately differentiated grade (P=0.023), I/II stage (P=0.014) and with no lymph node metastasis (P=0.016). Moreover, statistically significant differences in overall survival (OS) were found among 15-PGDH expression (log-rank test, P<0.001) and TNM stage (log-rank test, P=0.032). Most importantly, expression of 15-PGDH was found to be an independent predictive factor by multivariate analysis (Hazard ratio (HR) 0.315 [0.120-0.827], P=0.019). These findings indicated that NACT could increase 15-PGDH expression in advanced GC patients, and 15-PGDH may serve as a candidate prognostic biomarker of advanced GC response to NACT.     

4种生物学因子对局部晚期乳腺癌新辅助化疗疗效评估的价值

目的 探讨p53、ki67、nm23、表皮生长因子受体(EGFR)在局部晚期乳腺癌新辅助化疗疗效评估中的价值。 方法 选取2013年1月1日~2018年3月31日我院收治的局部晚期乳腺癌患者98例，检测新辅助化疗前后p53、ki67、nm23、EGFR的变化及其与临床疗效的关系。 结果 化疗后的p53、ki67、EGFR阳性表达均较化疗前降低，nm23阳性表达均较化疗前升高，差异均有统计学意义（P<0.05）。p53阳性者的有效率低于阴性者，差异有统计学意义（P<0.05）；ki67、nm23阳性者的有效率均高于阴性者，差异均有统计学意义（P<0.05）；EGFR阳性者与阴性者的有效率差异无统计学意义（P>0.05）。 结论 新辅助化疗能够显著改善局部晚期乳腺癌患者生物学因子p53、ki67、EGFR、nm23的表达，同时p53、ki67、nm23对评估化疗疗效具有一定价值。     

Utility of cytologic specimens in the evaluation of prognostic and predictive factors of breast cancer: current issues and future directions

Although numerous biological and molecular markers of breast cancer have been identified over the past two decades, traditional factors such as estrogen receptor (ER), progesterone receptor (PR), and HER-2 remain among the most useful indicators of prognosis and therapeutic response to treatment. These markers can be reliably evaluated in cytologic specimens, particularly in fine-needle aspirates (FNA) of primary or metastatic breast cancer. Accurate assessment of ER, PR, and HER-2 is critical in the treatment of breast cancer patients. A review of the literature, however, shows considerable interlaboratory variability in the detection of these markers and reporting of the test results. Because therapies are now being directed toward individual molecular targets, there is a need for increased standardization of such analyses. Current practices should follow consensus recommendations set by the College of American Pathologists and the American Society for Clinical Oncology, and the results should be monitored through quality-assurance programs. The utility of cytologic specimens of breast lesions is also not limited to evaluation of individual prognostic and predictive factors. Cytologic specimens have been used successfully for genomic and proteomic studies. Such investigational studies are under way and offer great potential for revolutionizing the prediction of patient outcomes and disease response to therapy, as well as assessment of risk of developing breast cancer.     

The prognostic and predictive power of redox protein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) π, θ and α, catalase and manganese superoxide dismutase. GST π (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P=0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments.     

Analysis of the relevance between molecular subtypes and efficacy of neoadjuvant chemotherapy in breast cancer as well as its prognostic factors

Background

Accurate pathological assessment of breast specimens after NACT is crucial. It is beneficial to determine the treatment efficacy and predict prognosis. So we should explore the relevance between molecular subtypes and efficacy of neoadjuvant chemotherapy in breast cancer as well as its prognostic factors, which about survival analysis and disease free survival involved, which was one part of contributing for evaluating in terms of global survival and disease free survival.

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.     

乳腺癌新辅助化疗的临床意义和病理学评价

一、乳腺癌新辅助化疗的定义 自1990年以来,国内肿瘤外科医师借鉴国外乳腺癌治疗的先进经验,开始对可手术的乳腺癌治疗方案进行改革,在术前先行化疗,再施行改良根治术,这种新的治疗模式大大减少了乳腺癌根治术的使用,也降低了手术对患者身体的创伤程度,提高了患者的生活质量.     

乳腺癌新辅助化疗组织学疗效评价研究

目的 探讨乳腺癌新辅助化疗后根治标本的组织学疗效评价标准.方法 收集2005年6月至2007年6月乳腺癌新辅助化疗154例档案,其中改良根治术139例,保乳手术15例.化疗结束后4周内实施乳腺根治术.按照Miller and Payne(MP)分级系统的标准规范进行取材、制片和按该系统组织学疗效评价标准进行分级评价,同时与既往应用的肿瘤治疗反应评价系统(既往评价系统)进行比较.对所有病例进行常规随访.应用SPSS 13.0软件进行统计学处理.结果 (1)154例手术标本所获得的组织学疗效评价信息:MP分级系统1级12例(7.8%)、2级33例(21.4%)、3级64例(41.6%)、4级31例(20.1%)、5级14例(9.1%);既往评价系统分别为轻度治疗反应51例(33.1%)、中度治疗反应71例(46.1%)、重度治疗反应32例(20.8%).MP分级系统与既往评价系统各组病例比例之间存在统计学相关(X2=186.660,P<0.01).(2)154例患者中147例获得随访信息(95.5%),随访时间16～38个月;其中14例出现术后复发、远处转移或死亡.MP分级系统5个级别组与患者生存状态均相关(X2=11.612,P=0.020),既往评价系统3个级别组与患者生存状态均无关(X2=0.881,P=0.644).结论 MP分级系统可以用于肿瘤化疗后的组织学疗效评价,与预后相关.     

乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

乳腺癌新辅助化疗后临床评价与病理评价的差异分析

目的 探讨乳腺癌新辅助化疗后,临床疗效评价与病理评价之间存在差异的病理学基础.方法 收集中国医学科学院肿瘤医院2005年6月至2007年12月施行乳腺癌新辅助化疗的209例.新辅助化疗前均行核芯针穿刺活检.化疗结束后4周内实施乳腺癌根治术.新辅助化疗前后均对乳腺原发灶进行临床体检、乳腺X线检查和(或)超声检查.实施新辅助化疗后,依实体瘤的疗效评价标准(RECIST,1.1版)对乳腺癌原发灶进行临床疗效评价,依Miller和Payne(MP)分级系统进行病理评价.应用SPSS 15.0软件分析临床评价与病理评价的相关性.结果 (1)新辅助化疗后依临床体检结果进行临床评价:完全缓解33例,部分缓解124例,疾病稳定41例,疾病进展11例.(2)新辅助化疗前后均行乳腺X线检查87例,依乳腺X线检查进行临床评价:完全缓解8例,部分缓解42例,疾病稳定37例.(3)新辅助化疗后MP分级病理评价:1级14例,2级35例,3级106例,4级36例,5级18例.(4)临床体检相关的临床评价与病理评价存在统计学相关性(x2=33.668,P=0.001),乳腺X线检查相关的临床评价与病理评价存在统计学相关性(x2=22.404,P=0.004).(5)新辅助化疗病理评价与X线检查相关临床评价存在差异的病理学改变有:残存浸润癌以脉管瘤栓为主要表现形式;伴有大片黏液湖形成的黏液腺癌;导管内癌残存,伴明显沙砾样钙化及周围组织的沙砾样钙化;间质结节状纤维化等.结论 乳腺癌新辅助化疗的临床评价与病理评价存在统计学相关性.两者之间的差异有相应的病理学基础.伴有大片黏液湖形成的黏液腺癌、导管内癌的残存伴沙砾样钙化及间质结节状纤维化可能是临床评价低估治疗疗效的原因之一;而残存癌表现为脉管瘤栓可能是临床评价高估治疗疗效的原因之一.     

新辅助化疗乳腺癌病理标本的处理对策及报告规范

新辅助化疗(neoadjuvant clhemotherapy)是指在进行手术治疗前对肿瘤患者进行化疗的一种治疗方法.1973年,米兰癌症中心的研究者首先采用新辅助化疗对失去手术机会的乳腺癌患者进行治疗,以期缩小肿块从而使患者有机会接受手术或放射治疗 [1].与常规化疗相比,新辅助化疗具有以下一些特点:(1)约80%的患者化疗后肿块缩小,原本失去手术机会的乳腺癌患者可重获手术机会;一些原本需施行乳房全切除的患者可进行保乳治疗,虽然这些患者的局部复发率可能升高,但其存活率与先手术后化疗的患者相当.     

Breast cancer spatial heterogeneity in near-infrared spectra and the prediction of neoadjuvant chemotherapy response

We describe an algorithm to calculate an index that characterizes spatial differences in broadband near-infrared [(NIR), 650-1000 nm] absorption spectra of tumor-containing breast tissue. Patient-specific tumor spatial heterogeneities are visualized through a heterogeneity spectrum function (HS). HS is a biomarker that can be attributed to different molecular distributions within the tumor. To classify lesion heterogeneities, we built a heterogeneity index (HI) derived from the HS by weighing the HS in specific NIR absorption bands. It is shown that neoadjuvant chemotherapy (NAC) response is potentially related to the tumor heterogeneity. Therefore, we correlate the heterogeneity index obtained prior to treatment with the final response to NAC. From a pilot study of 15 cancer patients treated with NAC, pathological complete responders (pCR) were separated from non-pCR according to their HI (-44 ± 12 and 43 ± 17, p = 3 × 10(-8), respectively). We conclude that the HS function is a biomarker that can be used to visualize spatial heterogeneities in lesions, and the baseline HI prior to therapy correlates with chemotherapy pathological response.     

The predictive value of EGFR and HER-2/neu in tumor tissue and serum for response to anthracycline-based neoadjuvant chemotherapy of breast cancer

We investigated the predictive value of HER-2/neu and epidermal growth factor receptor (EGFR) in tumor tissue and prechemotherapy serum for histopathologic response in 108 patients with breast cancer undergoing neoadjuvant anthracycline-based chemotherapy.Response to chemotherapy, assessed by histopathologic classification of regression (grade 0 [no therapy effect] to 4 [no residual tumor]), correlated significantly with prechemotherapy serum HER-2/neu levels. Median prechemotherapy serum HER-2/neu levels were significantly higher in patients with regression grades 1 through 4 compared with those in patients with regression grade 0 (9.6 vs 8.55 ng/mL; P = .011; 95% confidence interval [CI], .009-.014). Median pretreatment serum HER-2/neu levels of patients with complete pathologic response (pCR) were significantly higher than in patients with moderate or no treatment response (10.95 vs 9.1 ng/mL; P = .041; 95% CI, .036-.046). Receiver operating characteristic curve analysis revealed a serum HER-2/neu value of more than 10.3 ng/mL to predict a pCR with 80% sensitivity and 69.4% specificity. There was no significant correlation of response with HER-2/neu and EGFR scores in tumor tissue or with serum EGFR levels.Results demonstrate prechemotherapy serum HER-2/neu to be a significant predictor of response to neoadjuvant anthracycline-based chemotherapy for breast cancer.     

Isolated limb perfusion with hyperthermia and chemotherapy: predictive factors for regional toxicity

OBJECTIVE:

Isolated limb perfusion combined with melphalan is an accepted treatment for obtaining locoregional control in advanced melanoma of the extremities and other malignant neoplasias restricted to the limb. This study aims to examine the factors associated with toxicity caused by the regional method. We considered the technical aspects of severe complications associated with the procedure in an attempt to diminish the patient morbidity that occurs during the learning curve.

METHODS:

We conducted a retrospective analysis of the records of patients who underwent perfusion at the AC Camargo Hospital in São Paulo, Brazil between January 2000 and January 2009. The Wieberdink scale was applied to classify local toxicity and its relation to clinical and laboratory variables.

RESULTS:

Fifty-eight perfusions were performed in 55 patients. Most patients (86.2%) presented a toxicity level between I and III. Grade V toxicity was seen in five cases (8.6%), four of which occurred in the first 2 years. Creatine phosphokinase, an important predictive factor for toxicity, had an average value of 231.8 for toxicity grades I-III and 1286.2 for toxicity grades IV-V (p = 0.001). There was a relationship between the melphalan dose and toxicity, which was 77 mg (25 to 130 mg) for toxicity grades I-II and 93.5 mg (45 to 120 mg) for toxicity grades IV-V (p = 0.0204).

CONCLUSION:

It is possible to prevent the toxicity associated with melphalan by adjusting the dose according to the patient''s body weight (especially for women and obese patients) and the creatine phosphokinase values in the postoperative period.     

Review of diagnostic,prognostic, and predictive biomarkers in melanoma

Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens. FISH, CGH, Decision-Dx, and other multi-marker assays have been combined to improve overall predictability. This review discusses some of the most promising nucleic acid based assays that can be obtained from tissue specimens to assist with diagnosis, prognostication, and prediction of treatment response.     

A critical appraisal of prognostic and predictive factors for common lung cancers

The outlook for patients with lung cancer remains poor despite advances in the understanding of the pathology and biology of this disease. To optimize treatment protocols prognostic data are essential. The current era with molecular research on mRNA expression analysis and proteomics will lead to a plethora of new molecular markers, which are likely to be correlated, at least in part, with each other and with disease activity, progression and survival. However, although the number of prognostic factors analysed in published systematic reviews on lung cancer is large, the scope of these factors in individual studies is often narrow. In daily practice prognostic factors other than general TNM staging are not implemented. To assess the efficacy of new prognostic factors for the management of individual patients with non-small cell lung cancer, studies with clinically relevant modelling are required. In this review arguments are provided to use a model combining radiological and histopathological growth rate, histopathological diagnosis and molecular characteristics as markers for metastatic capacity, tumour volume doubling time and expected response to targeted therapy. This may reveal time-related predictive information useful for treatment guidance of the individual patient.