The possible role of stromal cell stimulation in worsening the prognosis of a subset of patients with breast cancer

This review examines the evidence that a subset of patients with breast cancer have tumors that are stimulated to grow by host cells in the tumor stroma. The search for such a minority group was prompted by the following observations. Adjuvant chemotherapy which is immunosuppressive improves disease-free interval and survival, whereas non-specific immunostimulation worsens the prognosis. Intrinsic immune reactivity is associated with a poor prognosis. A subset of tumors with a bad prognosis has anaplastic cells, dermal lymphatic invasion and a moderate to intense lymphoplasmacytic stromal infiltrate. Evidence is reviewed that adjuvant chemotherapy may be beneficial by virtue of its immunosuppressive effects in addition to tumor kill of minimal residual disease.     

超声心动图三维斑点追踪技术对乳腺癌曲妥珠单抗治疗中心脏毒性评估的应用

  目的  探讨超声心动图三维斑点追踪技术对乳腺癌曲妥珠单抗治疗中心脏毒性评估的应用。  方法  选取昆明医科大学第一附属医院2020年11月至2022年7月收治的应用曲妥珠单抗治疗乳腺癌患者65例,分别在治疗后3个月、6个月、9个月、12个月后给予常规超声心动图及三维斑点追踪技术（three-dimensional speckle tracking technique,3D-STI）,观察不同时间点的心脏指标参数的差异,包括左室射血分数（LVEF）、左房容积指数（LAVI）、二尖瓣舒张早期血流速度/二尖瓣环舒张早期移动速度（E/Em）、二尖瓣环舒张早期移动速度/二尖瓣环舒张晚期移动速度（Em/Am）、二尖瓣环收缩期移动速度（Sm）、二尖瓣舒张早期血流速度（E峰）、二尖瓣舒张晚期血流速度（A峰）、二尖瓣舒张早期环移动速度（Em）、二尖瓣舒张晚期环移动速度（Am）、左室扭转（LVtw）、左室整体纵向应变（GLS）、整体环周应变（GCS）、整体径向应变（ GRS）、整体面积应变GAS ）指标。  结果  治疗后3个月、6个月、9个月、12个月相关参数和治疗前相比,LAVI、E/Em、Am有所升高,Em/Am和Em有所下降,LAVI和E/Em之间呈正相关性;与治疗前相比,治疗后3个月、6个月、9个月、12个月的LVEF、GLS、GRS、LVtw、GCS、GAS均有所下降（P < 0.05）。  结论  乳腺癌患者应用曲妥珠单抗治疗时应用超声心动图三维斑点追踪技术效果理想,可以早期、准确对心脏毒性情况进行判断,可以为早期治疗提供参考依据,改善预后、临床结局方面价值显著。     

长链非编码RNA lnc-CCDC33-1:1在甲状腺乳头状癌中的表达及临床意义

目的：检测lnc-CCDC33-1:1在甲状腺乳头状癌（PTC）中的表达,并分析其临床意义。方法：选取2021年11月至2022年3月杭州市萧山区第一人民医院收治的120例PTC患者,收集120例PTC组织及30例癌旁正常甲状腺组织。采用qRT-PCR检测lnc-CCDC33-1:1在PTC组织及癌旁组织中的表达。分析本地队列和TCGA队列中lnc-CCDC33-1:1表达水平与PTC患者临床病理因素的相关性。采用受试者工作特征（ROC）曲线评价lnc-CCDC33-1:1对PTC的诊断价值。结果：与癌旁正常甲状腺组织比,lnc-CCDC33-1:1在PTC组织中表达明显升高（P ＜0.001）。ROC曲线显示曲线下面积为0.803（95%CI =0.736～0.869,P ＜0.001）。本地队列显示lnc-CCDC33-1:1 表达与PTC肿瘤大小（P =0.048）、腺外侵犯（P =0.019）、T分期（P =0.011）和淋巴结转移（P =0.009）相关,TCGA组数据显示lnc-CCDC33-1:1表达水平与PTC腺外侵犯（P =0.036）和淋巴结转移（P ＜0.001）相关。结论：lnc-CCDC33-1:1在PTC中表达异常升高,与PTC高危特征相关,可能是潜在的诊断标志物和治疗靶点。     

血清Tg、TgAb对甲状腺癌根治术联合131I治疗后随访期间复发/转移的评估价值

目的 研究血清甲状腺球蛋白（Tg）、甲状腺球蛋白抗体（TgAb）对甲状腺癌根治术联合¹³¹I治疗后随访期间复发/转移的评估价值。方法 回顾性分析2018年6月—2020年6月中国贵航集团三〇二医院收治的106例分化型甲状腺癌患者的临床资料,患者均接受甲状腺癌根治术治疗,术后均采用¹³¹I进行清除残留的甲状腺组织（清甲）治疗。随访24个月,将患者分为复发转移组（21例）和未复发转移组（85例）。比较两组临床资料、¹³¹I治疗情况及血清促甲状腺激素（TSH）、Tg、TgAb。绘制受试者工作特征（ROC）曲线分析血清Tg、TgAb检测对甲状腺癌根治术联合¹³¹I治疗后复发/转移的预测价值。采取非条件一般Logistic回归模型进行多因素分析。结果 与未复发转移组比较,复发转移组原位肿瘤T₄分期、手术方式为腺叶切除或近全切、残余甲状腺质量≥1 g、手术至¹³¹I治疗时间> 3个月、24 h摄¹³¹I率≤ 20%患者的占比均较高（P <0.05）;复发转移组血清Tg和TgAb水平均较高（P <0.05）;ROC曲线分析结果显示：血清Tg预测甲状腺癌根治术联合¹³¹I治疗后复发或转移的最佳截断值为1.674 μg/L,AUC为0.803（95% CI：0.721,0.884）,敏感性为81.1%（95% CI：0.724,0.898）,特异性为63.8%（95% CI：0.585,0.691）;血清TgAb预测的最佳截断值为44.19 3 IU/mL,AUC为0.911（95% CI：0.859,0.963）,敏感性为89.2%（95% CI：0.813,0.971）,特异性为72.5%（95% CI：0.674,0.774）。非条件Logistic一般回归分析结果显示：原位肿瘤T₄分期［O^R=2.916（95% CI：1.325,6.417）］、腺叶切除或近全切［O^R=3.243（95% CI：2.174,4.838）］、残余甲状腺质量≥ 10 g［O^R=1.835（95% CI：1.514,2.224）］、手术至¹³¹I治疗时间> 3个月［O^R=1.962（95% CI：1.371,2.808）］、24 h摄¹³¹I率≤ 20%［O^R=2.638（95% CI：1.219,5.709）］、血清Tg ≥ 1.674 μg/L［O^R=2.503（95% CI：1.430,4.360）］、血清TgAb≥ 44.193 IU/mL［O^R=2.944（95% CI：2.016,4.299）］可能是甲状腺癌根治术联合¹³¹I治疗后复发或转移的危险因素（P <0.05）;风险因素预测模型预测甲状腺癌根治术联合¹³¹I治疗后复发/转移的ROC曲线下面积为0.961（95% CI：0.935,0.987）,标准误为0.010,临界值为73.162,敏感性为91.9%（95% CI：0.863,0.957）,特异性为88.2%（95% CI：0.845,0.922）。结论 甲状腺癌根治术联合¹³¹I治疗后出现复发/转移的患者血清Tg、TgAb水平明显升高,Tg、TgAb对预测复发/转移具有较好的价值,联合其他危险因素建立风险因素预测模型可进一步提高预测价值。     

Expression of luminal and basal cytokeratins in human breast carcinoma

We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14. Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed. The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age. In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age. Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval. We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease. Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases. These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance.     

Light and Electron Microscopic Study of an Invasive Cribriform Carcinoma with Extensive Microcalcification Developing in a Breast with Silicone Augmentation

Although recent epidemiologic studies suggest that silicone augmentation of the breast is not associated with an increased risk of mammary carcinoma, cases of breast carcinoma arising in augmented breasts are being increasingly encountered as a large number of patients who had augmentation are getting older. A case of a 51-year-old woman with a 20-year history of breast augmentation who developed an invasive cribriform carcinoma associated with extensive microcalcification is presented. The patient had submammary silicone implants 20 years ago that were replaced, because of local complications, in subpectoral positions 10 years later. Dispersive X-ray microanalysis failed to demonstrate silicone in sections of the tumor and adjacent breast tissue. Appropriately fixed tumor tissue was available for electron microscopic examination. The tumor cells were rich in mitochondria, and their luminal surfaces were endowed with abundant microvilli, but the cell surfaces that came closest to the calcified microspheriols were devoid of microvilli and had cellular buddings between the microspheriols. It is suggested that the tumor cells might have been actively involved in the process of microcalcification.     

Complex CGH alterations on chromosome arm 8p at candidate tumor suppressor gene loci in breast cancer cell lines

Loss of genetic material from chromosome arm 8p occurs frequently in human breast carcinomas, consistent with this region of the genome harboring one or more tumor suppressor genes (TSGs). We used the complementary techniques of microsatellite-based LOH, high-density FISH, and conventional CGH on 6 breast cancer cell lines (MCF7, SKBR3, T47D, MDA MB453, BT549, and BT474) to investigate the molecular cytogenetic changes occurring on chromosome 8 during tumorigenesis, with particular emphasis on 6 potential TSGs on 8p. We identified multiple alterations of chromosome 8, including partial or complete deletion of 8p or 8q, duplication of 8q, and isochromosome 8q. The detailed FISH analysis showed several complex rearrangements of 8p with differing breakpoints of varying proximity to the genes of interest. High rates of LOH were observed at markers adjacent to or within PCM1, DUSP4/MKP2, NKX3A, and DLC1, supporting their status as candidate TSGs. Due to the complex ploidy status of these cell lines, relative loss of 8p material detected by CGH did not always correlate with microsatellite-based LOH results. These results extend our understanding of the mechanisms accompanying the dysregulation of candidate tumor suppressor loci on chromosome arm 8p, and identify appropriate cellular systems for further investigation of their biological properties.     

The detection of early breast cancer: three-year results from a diagnostic breast clinic

The initial results from a diagnostic breast clinic in which clinical examination, x-ray mammography and ultrasound are used to establish a diagnosis during a single patient-visit are described. In 3461 patient-visits, 82 histologically-proven breast cancers were detected. Fifty-two per cent of these cancers were 2 cm or less in diameter and 61% had no axillary lymph-node metastases. Fifteen cancers were impalpable lesions which were detected by mammography alone. The over-all malignant-to-benign biopsy ratio was 1:2.7; for impalpable tumours, this ratio was 1:3.9. The role of such a diagnostic breast clinic is discussed, and attention is drawn to a relatively low attendance of women in the "high-risk" age group of over 50 years of age.