Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

Vascular Endothelial Growth Factor Expression in Invasive Ductal Carcinoma of Breast

Objective： To detect the expression of VEGF and MVD count in invasive ductal carcinoma of breast to clarify the association of VEGF expression and MVD count with the clinicopathologic features. Methods： The expressions of VEGF, ER, PR, C-erbB-2 and MVD count in 88 cases of invasive ductal carcinoma of breast were examined by immunohistochemistry staining （SP-method）. Results： Sixty-two out of the eighty-eight specimens of breast carcinoma （70.45%） showed positive expression of VEGF. The positive rate of VEGF in cases with lymph node metastasis was higher than that without lymph node metastasis （P〈0.05）. The positive rate of VEGF in stage IIb-Ⅲ was higher than that in stage Ⅰ-Ⅱa （P〈0.05）. The positive rate of VEGF in C-erbB-2 positive group was higher than that in C-erbB-2 negative group （P〈0.05）. Higher expression of VEGF was observed in cases with higher tissue differentiation degree （P〈0.05）. Also, significant higher MVD count was observed in cases with higher tissue differentiation degree （P〈0.01）. The MVD count increased significantly with the increase of the expression of VEGF （P〈0.01）. Conclusion： The result of this study suggested that in invasive ductal carcinoma of breast, angiogenesis and metastasis were mediated mainly by VEGF. The expression of VEGF and MVD might be reference predictors for the biological behavior of breast carcinoma. The antiangiogenic therapy which used VEGF as a target would become a new method to treat patients who were C-erbB-2 positive in the future.

Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia （FEA）, atypical ductal hyperplasia （ADH）, and lownuclear grade ductal carcinoma in situ （DCIS）. The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low- nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations--most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.

MTDH Expression in Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To clarify the expression of MTDH in invasive micropapillary carcinoma of the breast （IMPC） and analyze the relationship between MTDH expression and clinicalpathologic parameters of the IMPC patietns.

Inverted Apical CD24 and Weak EZH2 Expressions Are Phenotypic Characteristics of Pure Invasive Micropapillary Carcinoma of the Breast

Invasive micropapillary carcinomas (IMPC) of the breast account for less than 2% of all breast cancers and have been recently described as luminal B carcinomas. CD24, CD44, ALDH1 and EZH2 are commonly used as stem-cell markers that display differential expression as a function of stage and molecular type, but their pattern of expression according to this rare histological type remains poorly defined and unknown for EZH2. We assessed expression of these markers in a series of 28 micropapillary breast carcinomas and compared the results with those obtained in a series of luminal A (27 cases) and B (34 cases) invasive carcinomas not otherwise specified (IC-NST). CD24 and CD44 were expressed in most cases. However, CD24 was expressed at the inverted apical membrane in 85% of invasive micropapillary carcinoma and at the apical pole of gland-forming cells in 45% of luminal A (p-val = 6.8 × 10-4) and 13% of luminal B cases (p-val = 1.1 × 10-7). ALDH1 was expressed in the stroma in most tumors, but in only 25%, 11% and 15% in epithelial cells of IMPC, luminal A and B IC-NST, respectively. Nuclear expression of EZH2 was not observed in luminal A tumors, and was detected in 35% (12/34) of luminal B carcinomas (p-val = 6.1 × 10-3) and only 4% (1/28) of invasive micropapillary carcinomas. This series shows that invasive micropapillary carcinomas harbor a CD24-positive inverted apical pole associated with weak EZH2 expression, phenotypical characteristics that distinguish this entity from other luminal carcinomas.

Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.

Gastrointestinal metastasis secondary to invasive lobular carcinoma of the breast:A case report

BACKGROUND Gastrointestinal metastasis of breast cancer is rare,and clinicians may not have previously encountered this disease in clinical practice.CASE SUMMARY We report a patient with invasive lobular carcinoma of the breast who developed gastrointestinal metastasis two years after modified radical surgery.Mild elevation of carbohydrate antigen 15-3 was observed in the patient at an early stage;however,diagnosis and treatment were delayed due to non-specific clinical manifestations and no identifiable metastasis observed on imaging.CONCLUSION Clinicians should pay attention to gastrointestinal metastasis of breast cancer,especially invasive lobular carcinoma of the breast.

Immunohistochemical analysis of 8 biomarkers on tissue microarray (TMA) of 46 Moroccan invasive breast carcinoma

Aim of the study: Immunohistochemical evaluation of hormone receptors, Her2/neu, CK5/6, E-cadherin, beta-catenin, p53 and PTEN on Tissue Micro Array (TMA) of 46 Moroccan invasive breast carcinomas. Materials and Methods: The cases comprised 40 invasive ductal carcinomas, 4 invasive lobular carcinomas, 1 mixed carcinoma and 1 invasive colloid carcinoma. TMA paraffin blocs were prepared with the Beecher manual arrayer and immunostaining was performed using standard immunoperoxidase techniques. Results: 58.69% of the cases were ER positive. 43.18% (19/44) were triple negative breast cancers (TNBC) of which 15.78% (3/19) were of the basal phenotype expressing CK5/6. On the other hand, 72.22% (13/18) of the TNBC cases were IDC grade 3. Of the 18 IDC grade 3, 22.22% (4/18) were CK5/6 positive. 41.30% and 10.86% of the cases showed reduced expression of E-cadherin and beta-catenin respectively. Beta-catenin nuclear and cytoplasmic staining was noted in 20% and 97.82% respectively. p53 was overexpressed in 10.86% of the cases whereas PTEN loss or reduced expression was noted in 86.95% of the cases. Conclusion: The aim of our study was to introduce TMA technique in our hospital which is considered a reference institution for cancer in Morocco. Although no statistical study was performed to look for any significance of the results obtained, we found good correlation with some of the data in the literature. To determine the molecular characteristics, if any, of the Moroccan patient, larger multidisciplinary and prospective studies would be interesting in the aim to personalize therapeutic decisions.

Clinical Value Analysis of Ultrasonography and MRI in Diagnosis of Invasive Micropapillary Carcinoma of Breast

Objective:To investigate the diagnostic value of invasive micropapillary carcinoma(IMPC)by ultrasonography and MRI.Method:63 female patients with IMPC were selected,all of which were confirmed by pathological examination,and were assigned to the IMPC group.In the same period,40 patients with invasive ductal carcinoma(IDC group)were selected for diagnostic efficacy control.The efficacy indexes of accuracy,sensitivity,specificity,positive prediction rate and negative prediction rate were 73.0%,65.9%,89.5%,93.5%,46.9%,respectively.The efficiency indexes of accuracy,sensitivity,specificity,positive prediction rate and negative prediction rate of ultrasound combined with breast MRI were 93.6%,93.2%,94.7%,97.6%,85.7%.Ultrasonography combined with MRI has more application value in the diagnosis of IMPC.

Clinical and pathological characteristics of intraductal proliferative lesions and coexist with invasive ductal carcinomas

Objective： The purpose of this study was to study the clinical and pathological characteristics of breast intraductal proliferative lesions （IDPLs） and associated with invasive breast cancer. Methods： We reviewed 327 cases of breast intra- ductal proliferative lesions including 53 cases of usual ductal hyperplasia, 57 cases of atypical ductal hyperplasia, 89 cases of ductal carcinoma in situ, and 128 cases coexist with invasive ductal carcinomas. Cases of pure invasive cancer without intraductal proliferative lesions were excluded. The mult IDPLs biological parameters including the express of ER, PR, HER2, HIF-lo and Ki-67 detected by immunohistochemistry S-P method （n = 327） and the levels of CA153, TSGF, CA125 and CEA both in nipple discharge and serum （n = 179） measured with Electrochemiluminescence method and their relationship were studied, and 30 cases of normal pregnant women were compared with. Results： A single histologic subtype was present in 49.85% （163/327） of the cases, two subtypes in 33.03% （108/327）, and three in 17.13% （56/327）. The most common subtypes present were cribriform （43.12%, 141/327） and solid （38.53%, 126/327）, while the comedo （16.35%, 54/327）, and micropapillary （12.84%, 42/327） subtypes were less common. Comedo and solid were frequently found together for coexpres- sion as were micropapillary and papillary subtypes. However, Comedo subtype was much less likely to be found with papillary, cribriform or micropapillary subtypes. Additionally, comedo subtypes tend to be hormone receptor negative, Her2 positive and high-grade while the cribriform and solid subtype tends to be hormone receptor positive, Her2 negative and low grade. Papil- lary subtype was least likely to be associated with an invasive cancer. Furthermore, the nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in coexist with invasive ductal carcinomas patients were significantly higher than those in the benign breast disease （pure intraductal proliferative lesions） and normal pregnant women （P 〈 0.01）. Additionally, the levels of CA153, TSGF, CA125 and CEA in nipple discharge were significantly higher than in the serum （P 〈 0.01）, and had a positive correlation with the Ki-67, grade, clinical stage, lymph node metastasis and tumor recurrence （P 〈 0.05）, and negative correla- tion with the level of ER and PR （P 〈 0.05）. The sensitivity of the four serum tumor markers in combination was only 69.77%, in contrast, the combined detection both in discharge and serum was 97.67%, and the negative predictive value was 99.03%. The sensitivity of combined detection both in nipple discharge and serum were significantly higher than other detection （P 〈 0.05）. Conclusion： IDPLs often present more than one histologic subtype and the most common subtypes are cribriform and solid, while comedo and micropapillary subtypes are less common. Our results suggest that the levels of CA153, TSGF, CA125 and CEA in nipple discharge were significantly higher than those in the serum, and is associated with HIF-le. The aberration of HIF-la may play a key role during oncogenesis and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. Nipple discharge can be the earliest presenting symptom of breast cancer. The dynamic combined detection of the four tumor markers both in nipple discharge and serum are helpful to the stratification of preoperative patients and benefit to better prewarning markers for monitoring their recurrence and metastasis and clinical staging of tumors in clinic, but cannot increase the sensitivity of judging the patients with early breast cancer.

Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor （VEGF） and CD105-microvessel density （MVD）in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expression. Positively stained microvessels were counted in dense vascular loci under 400x magnification, MVD in the peripheral area adjacent to the lesion and in the central, area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue （22.0%, P 〈 0.05）. There was a positive correlation between VEGF overexpression and histological grade, lymph node metastasis, and distant metastasis of invasive breast cancer. VEGF expression was not related to age or size of the tumor （P 〉 0.05）. MVD of the peripheral area adjacent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benignbreast disease groups （P 〈 0.01 for each group）. There were significant differences in the mean CD105-MVD, between invasive breast tumors with a histological grade of Ⅰ or Ⅱ and grade Ⅲ; between tumors with lymph node or distant metastasis; and between patients with or without recurrence （P 〈 0.05）. However, there was no difference in the mean MVD between the two age groups （≤ 50 years vs. 〉 50 years） or the two tumor diameter groups （〈 2 cm vs. 〉 2 cm）, P 〉 0.05. Conclusion Overexpression of VEGF and MVD may be important biological.markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor markers could provide better prognostic monitoring for disease recurrence and metastasis, as well as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as well as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better follow-up regimens and appropriate treatment strategies for breast cancer patients.

Enhancing Breast Cancer Diagnosis with Channel-Wise Attention Mechanisms in Deep Learning

Breast cancer,particularly Invasive Ductal Carcinoma(IDC),is a primary global health concern predominantly affecting women.Early and precise diagnosis is crucial for effective treatment planning.Several AI-based tech-niques for IDC-level classification have been proposed in recent years.Processing speed,memory size,and accuracy can still be improved for better performance.Our study presents ECAM,an Enhanced Channel-Wise Attention Mechanism,using deep learning to analyze histopathological images of Breast Invasive Ductal Carcinoma(BIDC).The main objectives of our study are to enhance computational efficiency using a Separable CNN architecture,improve data representation through hierarchical feature aggregation,and increase accuracy and interpretability with channel-wise attention mechanisms.Utilizing publicly available datasets,DataBioX IDC and the BreakHis,we benchmarked the proposed ECAM model against existing state-of-the-art models:DenseNet121,VGG16,and AlexNet.In the IDC dataset,the model based on AlexNet achieved an accuracy rate of 86.81%and an F1 score of 86.94%.On the other hand,DenseNet121 outperformed with an accuracy of 95.60%and an F1 score of 95.75%.Meanwhile,the VGG16 model achieved an accuracy rate of 91.20%and an F1 score of 90%.Our proposed ECAM model outperformed the state-of-the-art,achieving an impressive F1 score of 96.65%and an accuracy rate of 96.70%.The BreakHis dataset,the AlexNet-based model,achieved an accuracy rate of 90.82%and an F1 score of 90.77%.DenseNet121 achieved a higher accuracy rate of 92.66%with an F1 score of 92.72%,while the VGG16 model achieved an accuracy of 92.60%and an F1 score of 91.31%.The proposed ECAM model again outperformed,achieving an F1 score of 96.37%and an accuracy rate of 96.33%.Our model is a significant advancement in breast cancer diagnosis,with high accuracy and potential as an automated grading,especially for IDC.

Metastatic Lobular Carcinoma of the Breast Presenting with Small Bowel Metastases:Case Report and Literature Review

Introduction: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, representing 5% to 15% of invasive tumors. ILC tends to spread to bones, lungs, central nervous system, reproductive organs, and the gastrointestinal tract (GI tract). The most commonly affected organs in the GI tract are the stomach, small intestine, followed by colon and rectum. Case presentation: A 78-year-old woman who was referred to our institution after having a bowel obstruction that required a diagnostic laparoscopy where they identified an obstructing ulcerative lesion in the distal ileum that was managed with a segmental bowel resection. Pathology report showed an invasive lobular breast carcinoma that occluded 90% of the bowel lumen. A PET/CT scan revealed a left breast tumor with increased metabolism. The patient was staged as a clinical cT4b, cN0, cM1 left breast invasive lobular carcinoma (ER/PgR positive, HER-2 negative). She was managed with endocrine therapy with Letrozole (an eight-week course). A follow-up PET/CT showed a peritoneal hypermetabolic nodule adjacent to the previous ileal anastomosis. The lesion decreased in size and metabolic activity. In a multidisciplinary fashion, the endocrine therapy was extended for another three months. Another follow-up PET/CT scan was performed three months after the identification of the peritoneal implant that showed that the nodule increased in size and in metabolism. The lesion continued to decrease significantly in size and became metabolically inactivity. Due to the good breast response and the possibility that the ileal nodule could be a granuloma, she underwent an exploratory laparoscopy with excision of the peritoneal nodule, and a modified left radical mastectomy with immediate breast reconstruction (complex wound closure). The final pathology report of the nodule was negative for malignancy. She continued on endocrine therapy and underwent whole breast irradiation four weeks after the operation. Currently, she is free of disease with no evidence of local, regional, or distant recurrence, and she is still on endocrine therapy. Discussion: The time interval between primary breast cancer and gastrointestinal involvement may range from synchronous presentation to as long as 30 years. The clinical manifestations in GI lobular breast cancer metastasis may range from non-specific complaints to acute GI symptoms, such as a bowel obstruction. There are multiple controversies in the management of ILC. Systemic treatment should be initiated as soon as possible. Indications for postmastectomy radiotherapy are also controversial, given the propensity for multifocal/multicentric tumors and late recurrences, sometimes in atypical locations. Five years of postoperative adjuvant hormonal therapy is an option for women with poor prognosis. Remissions are observed in 32% to 53% of patients. Conclusion: Metastatic lobular carcinoma of the breast has a wide range of clinical presentations. Patients with a history of breast cancer who present with new GI tumors should have these lesions evaluated for evidence of metastasis through histopathologic and immunohistochemical analysis, this will allow for appropriate management. Currently, breast cancer management involves a multidisciplinary approach including surgery, radiotherapy, and systemic medical therapy, and the treatment must be tailored to the patient’s needs.

乳腺浸润性微乳头状癌患者的临床病理特征分析

目的 探讨乳腺浸润性微乳头状癌(invasive micropapillary carcinoma,IMPC)的临床和病理特征。方法 选取2015年3月至2023年3月首都医科大学宣武医院行乳腺癌根治性手术的IMPC患者55例,根据病理诊断学分类中是否伴有其他类型乳腺恶性肿瘤,分为单纯组(n=10)和混合组(n=45),收集并分析患者的临床和病理资料。结果55例患者平均年龄(57.6±12.4)岁,平均肿瘤大小2.0(1.5,3.6)cm,54例(98.2%)患者的免疫组化的雌激素受体(estrogen receptor,ER)和孕酮受体(progesterone receptor,PR)均为阳性,49例(89.1%)患者的人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)阴性。28例(50.9%)存在腋窝转移。25例(45.5%)存在脉管癌栓。与混合组相比,单纯组患者年龄更高[(60.3±17.5)岁比(57.0±11.1)岁],淋巴结转移总数更多[2.0(1.3,3.5)个比1.8(1.5,4.1)个],差异均有统计学意义(P<0.05)。IMPC患者镜下肿瘤细胞呈“桑葚状”细胞团结构,上皮膜抗原(epithelial membrane antigen,EMA)染色呈“极性倒置”特点。结论 IMPC患者淋巴结受累率较高,对于病理结果为IMPC的患者,应严格腋窝评估和清扫,以期为患者带来更大获益。

黄芩素对人乳腺癌细胞系MDA-MB-231侵袭、迁移、上皮间充质转化的调控作用及其机制

目的观察黄岑素对人乳腺癌细胞系MDA-MB-231的侵袭、迁移及上皮间充质转化(EMT)的调控作用,探讨其可能作用机制。方法取对数生长期MDA-MB-231细胞分为一组、二组、三组及对照组,一组、二组、三组分别加入2.5、5、10μmol/L的黄岑素,对照组不做任何处理。培养48 h时采用划痕修复实验观察四组细胞迁移能力、采用Transwell侵袭实验观察四组细胞侵袭能力,采用Western Blotting法检测细胞EMT标志物波形蛋白(vimentin)及E-钙黏蛋白(E-cadherin)、整合素αv、β3、磷酸化黏着斑激酶(p-FAK)、磷酸化磷脂酰肌醇3激酶(整合素p-PI3K)。结果与对照组相比,黄岑素组细胞迁移率降低、侵袭细胞数少,细胞E-cadherin相对表达量高,vimentin、整合素αv、整合素β3、p-FAK、p-PI3K蛋白相对表达量低,且呈剂量依赖性(P均<0.05)。结论黄芩素抑制MDA-MB-231细胞的侵袭、迁移及EMT。黄岑素可能通过抑制整合素αv、整合素β3表达,进一步抑制p-FAK、p-PI3K蛋白表达,抑制MDA-MB-231的侵袭、迁移及EMT。

HRD1、P53、HER2水平与乳腺浸润性导管癌临床病理特征的关系

目的研究HRD1、P53,HER2与乳腺浸润性导管癌临床病理特征的关系。方法选取确诊并实施相关治疗的82例乳腺癌患者为此次试验的对象,收集全部患者的癌旁组织以及癌组织石蜡切片,应用免疫组织化学EliVi-sion两步法比较癌旁组织以及癌组织中HRD1、P53、HER2水平,分析HRD1、P53、HER2与乳腺浸润性导管癌临床病理特征的相关性。结果癌组织中HRD1(χ^(2)=5.502,P=0.019)、P53(χ^(2)=6.552,P=0.011)、HER2(χ^(2)=5.512,P=0.023)的阳性表达率显著高于癌旁组织;脉管侵犯有无、不同肿瘤直径、TNM不同分期以及淋巴结是否发生转移患者的P53、HRD1、HER2表达水平存在差异(P<0.05);相关性分析发现,患者的肿瘤直径、脉管侵犯、TNM分期以及淋巴结转移情况与患者的HRD1、P53、HER2水平呈正相关。结论HRD1、P53、HER2与乳腺浸润性导管癌临床病理特征呈现显著的相关性,可作为日后治疗的重要靶点。

乳腺导管原位癌、导管原位癌伴微浸润及浸润性导管癌的分子分型差异性

目的:研究乳腺导管原位癌(DCIS)、导管原位癌伴微浸润(DCIS-MI)及浸润性导管癌(IDC)不同临床病理特征及分子分型间的差异。方法:回顾性分析本院2015年01月至2022年06月经病理确诊的乳腺癌患者。分析其临床病理资料,包括患者的年龄、雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER-2)、肿瘤细胞增殖活性标记物(Ki-67)、分子分型。采用χ^(2)检验或Fisher确切概率法比较三组患者临床病理表现的差异性。结果:本研究共计选取患者1167例,其中DCIS组为180例(15.42%),DCIS-MI组为67例(5.74%),IDC组为920例(78.83%)。DCIS、DCIS-MI及IDC患者在ER、PR、HER-2、Ki-67中阳性分布及分子分型均有显著差异,具有统计学意义(P<0.05),DCIS-MI患者多以HER-2过表达型为主,ER、PR状态多呈阴性,HER-2多呈阳性,高核分级。DCIS患者多以Luminal A型为主,Ki-67多呈低表达。高核级别、HER-2过表达、ER阴性、PR阴性是影响并促进乳腺DCIS进展为DCIS-MI的预测因子。IDC患者多以Luminal B型为主,ER、PR状态多呈阳性,Ki-67多呈高表达。而在年龄分布上无差异,无统计学意义(P>0.05)。结论:乳腺DCIS、DCIS-MI及IDC间免疫组化标记物和分子分型分布不同,与DCIS相比,DCIS-MI核异型性多呈高核分级,ER、PR阴性比例多,HER-2过表达型比例多,考虑DCIS-MI是独立存在的一种病变,较DCIS有“质”的改变,提示两者处于乳腺癌进展的不同阶段。

数字化乳腺断层摄影对浸润性乳腺导管癌病灶大小测量准确性及影响因素分析

目的:探讨数字化乳腺断层摄影(digital breast tomosynthesis,DBT)评估浸润性乳腺导管癌(invasive mammary ductal carcinoma,IDC)病变大小的准确性,并分析其影响因素。方法:回顾性分析2019年03月至2022年08月在我院经手术病理确诊为IDC的145例患者的临床资料,所有患者术前均行DBT检查。以手术切除新鲜标本病理测量值为金标准,采用Spearman相关分析和Bland-Altman图比较DBT预估IDC病灶大小的相关性及一致性检验。采用多因素Logistic回归分析DBT测量IDC病灶大小不准确的预测因素。结果:DBT及病理测量病灶大小的中位数(四分位间距)分别为2.1(1.5,2.8)cm、2.5(2.0,3.0)cm。DBT检查测量病灶大小一致率为75.86%(110/145),低估病灶21.38%(31/145),高估病灶2.76%(4/145)。Spearman相关分析显示,DBT与病理测量IDC病灶大小呈中度正相关,r=0.575,P<0.001。Bland-Altman分析显示,DBT检查较病理金标准,略低估病灶大小,平均差值为-0.408 cm,95%CI为-0.559~-0.258。多因素Logistic回归分析显示,病理测量大小>2 cm及肿块形态不规则形是DBT测量IDC病灶大小不准确的独立危险因素(OR=8.110,95%CI为2.077~31.672,P=0.003;OR=0.301,95%CI为0.113~0.798,P=0.016)。结论:DBT检查测量IDC病灶大小与病理测量值呈中度相关,对IDC病灶大小测量一致率较高,可以作为IDC术前预估病灶大小的依据,但仍存在低估病灶大小的情况。病理测量大小>2 cm及肿块形态不规则形IDC更易出现测量病灶大小不准确。

乳腺富于脂质癌的探讨

乳腺富于脂质癌(LRC)于1963年被首次描述,该疾病已被重新分配到无特殊类型浸润性乳腺癌类别中。有研究者认为乳腺LRC癌细胞中的脂质是乳腺导管上皮细胞分泌产物。LRC的病理特征是质地坚硬,切片呈淡黄色,与周围组织边界不清。乳腺LRC通常被认为是乳腺癌的侵袭性表型,其缺乏统一的治疗方案和标准。更深入的随访研究将有助于制定综合治疗方案。该文评述了乳腺LRC的研究过程和发展现状。

乳腺包裹性乳头状癌3例报告并文献复习

目的探讨乳腺包裹性乳头状癌(EPC)临床病理特征、预后情况,以期加深理解EPC,并为EPC的诊治提供一些思路。方法回顾性分析扬州市妇幼保健院2021年1月至2022年12月收治的3例EPC病人的临床病理资料,同时结合相关文献进行系统复习。结果3例病人均为绝经后女性,发病年龄范围为57~64岁,肿瘤长径1.5~3.0 cm,均因发现乳房肿块就诊。超声多表现囊实性、混合性包块,边缘呈角或模糊,RI值均大于0.7;组织学多见扩张囊腔、厚纤维包膜,腔内乳头状病变为主,细胞成实性或筛状排列。免疫组化均示雌激素受体(ER)阳性(90%~100%)、孕激素受体(PR)阳性(80%~90%),增殖细胞核抗原(Ki-67)(5%~10%),肌上皮标志物钙调蛋白(Calponin)、细胞角蛋白(CK)5/6、p63阴性。其中,EPC伴浸润性导管癌(IDC)1例,EPC伴导管原位癌(DCIS)2例,均行患侧全乳房切除术加腋窝前哨淋巴结活检术,均未见淋巴结转移。EPC伴IDC病人术后行化疗、内分泌治疗,EPC伴DCIS病人术后行预防性内分泌治疗。随访11~27个月,病人均无局部复发、远处转移或死亡。结论EPC是一种好发于老年女性的罕见乳腺肿瘤,表现为恶性程度低、淋巴结转移少等惰性生物行为,预后一般较好。但仍需警惕EPC伴浸润性癌的可能,避免误诊、漏诊。其个体化、精准化治疗策略尚有待进一步深入研究。