Immunohistochemical analysis on biological markers in ductal carcinomain situ of the breast

BACKGROUND: The increasing use of mammographic screening has led to an increased detection of ductal carcinoma in situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed. METHODS: Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications. RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis. CONCLUSION: Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.     

Ductal carcinomain situ of the breast

Objective: To investigate the clinical characteristics, treatment and prognosis of ductal carcinomain situ (DCIS) of the breast. Methods: Clinicopathological and follow-up data were collected in 52 patients with DCIS. Results: The clinic data showed that 50 patients had signs of breast lumps or/and nipple discharges, 2 patients presented abnormal mammography; 2 patients had lymph node involved; and 14 patients were accompanied with intraductal papillomatosis. All patients were received surgical therapy. The follow-up data showed 1 patient locally recurred after lumpectomy, and was underwent mastectomy again, then cured. There were no patients died of DCIS. Conclusion: Mastectomy should be a standard surgical mode, and the prognosis of DCIS was favorable, but mammography for screening of asymptomatic women should be strengthened to find DCIS.     

Diagnosis of ductal carcinoma in situ (DCIS) and intraductal papilloma using fluorescence in Situ Hybridization (FISH) analysis

BACKGROUND: It is often difficult to pre-operatively diagnose ductal carcinoma in situ (DCIS)or intraductal papilloma (IDP). Current reports show that breast cancer frequently has numerical aberrations of chromosomes 1, 11 and 17. We investigated whether fluorescence in situ hybridization (FISH) analysis using three centromere-specific probes for chromosomes 1, 11 and 17 was feasible for diagnosing intraductal breast lesions. METHODS: Fine-needle aspiration specimens from 102 breast lesions including DCIS (10), invasive ductal carcinoma (IDC) (78), IDP (7), fibroadenoma (6) and mastopathy (1) were examined for numerical aberrations on chromosomes 1, 11, 17 using FISH. If over 15% of all cells showed one signal, the sample was judged monosomic. If over 20% of cells showed three or more signals, it was considered polysomic. If the specimen had an aberration of at least one chromosome, it was judged positive. RESULTS: Nine of 10 DCISs showed numerical aberrations of at least one chromosome whereas 65 of 78 IDCs and 2 of 14 benign lesions (containing 7 IDPs of which one case was positive) showed numerical aberrations on these chromosomes. The proportion of positive results was highest with DCIS. Moreover 6 out of 7 DCISs showed an aberration of all three chromosomes simultaneously and one case showed an aberration of two chromosomes. All aberrations in case of DCIS were polysomic while two benign lesions and 15 IDCs showed a monosomic pattern. CONCLUSION: FISH may enable more accurate diagnosis of intraductal breast lesions.     

Surgery for ductal carcinoma in Situ

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.     

Mucocele-like tumor of the breast caused by ductal carcinoma in situ: a case report

A mucocele-like tumor (MLT) of the breast caused by clinging and micropapillary carcinoma in situ is reported. The tumor was a smooth-contoured mass located near the nipple in the lower inner quadrant of the left breast. Ultrasonography showed a cystic tumor and distended ducts. An aspiration specimen contained abundant mucinous material and a small amount of epithelial cell components, but was insufficient for cytological diagnosis. An excisional biopsy specimen disclosed multiple cysts containing mucin with extravasation into the stroma. Additional pathologic diagnosis using consecutive microscopic sections demonstrated ductal carcinoma in situ. Subcutaneous mastectomy was subsequently performed. Histopathologic findings in the resected and biopsy specimens indicated a diagnosis of MLT caused by widely spreading clinging and micropapillary ductal carcinoma in situ. The ductal epithelium of the MLT in an open biopsy specimen must be carefully examined using consecutive microscopic sections to detect occult DCIS.     

Non-palpable and non-invasive ductal carcinoma with bloody nipple discharge successfully resected after cancer spread was accurately diagnosed with three-dimensional computed tomography and galactography

A case of ductal carcinomain situ (DCIS) that was treated by partial mastectomy is reported. The operation was performed after accurate estimation of cancer spread by three-dimensional computed tomography (3D-CT). The patient was a 39-year-old woman without a palpable lump who had a bloody nip-ple discharge. Ultrasonography showed distended mammary ducts with intraductal components. Fine needle aspiration cytology revealed ductal carcinoma. Galactography showed two subsegmental ducts and peripheral branches in the upper-inner quadrant of the right breast. 3D-CT depicted a well enhanced segmental-clumped lesion including two subsegments of a duct lobular system shown in galactograms. DCIS was diagnosed and partial mastectomy following the video assisted thoracoscopic surgery (VATS) marker insertion was performed, after cancer spread was accurately diagnosed by 3D-CT guidance. DCIS resected by minimally sufficient partial mastectomy with negative surgical margins was diagnosed histopathologically.     

A case of intracystic papillary carcinoma accompanying widespread ductal carcinomain situ

A 39-year-old Japanese woman noticed a right breast tumor in July 2004. Mammography (MMG) demonstrated an oval tumor without calcification. Dynamic Magnetic Resonance Imaging (D-MRI) demonstrated a high-intensity mass on T2-weighted images, showing mild enhancement during the arterial phase and persistent enhancement during the arterial late phase. Core needle biopsy revealed papillary carcinoma suggestive of Intracystic Papillary Carcinoma (IPC). Auchincloss operation was performed following a partial mastectomy, as the surgical margin after partial mastectomy was positive for carcinoma. Histopathologic mapping of her right breast revealed wide and extensive intraductal spread of DCIS around the IPC. IPC was originally reported to be a localized non-invasive mammary carcinoma. But approximately, half of IPC cases are associated with invasive carcinoma or DCIS beyond the tumor. Careful selection of operative procedure is needed after localized non-invasive IPC or IPC associated with DCIS around the main tumor or invasive carcinoma is diagnosed.     

乳腺导管原位癌和乳腺导管原位癌伴微浸润的分子分型差异性研究

背景与目的：乳腺导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCISMI）是乳腺导管原位癌（ductal carcinoma in situ,DCIS）发展到浸润性乳腺癌（invasive breast cancer,IDC）的中间阶段,该研究旨在分析乳腺DCIS和DCIS-MI这两类早期乳腺癌不同临床病理学特征和各个分子分型间的差异。方法：本回顾性研究纳入了317例DCIS患者,其中227例（71.6%）为纯DCIS患者,90例（28.4%）为DCIS-MI患者。所有患者根据其DCIS成分而非微浸润成分的免疫组织化学检查结果分成腔面A型［雌激素受体（estrogen receptor,ER）和（或）孕激素受体（progesterone receptor,PR）阳性,人类表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）阴性］、腔面B型［ER和（或）PR阳性,HER-2阳性］、HER-2过表达型（ER和PR阴性,HER-2阳性）和基底样型（ER和PR阴性,HER-2阴性）。结果：DCIS-MI患者的肿瘤大小倾向更大（P=0.059）,病理核分级显著更高（P=0.002）。和DCIS患者相比,乳腺DCIS-MI患者中腔面A型比例较低而基底样型比例较高（P=0.001）。结论：乳腺DCIS和DCIS-MI间分子分型分布不同,临床病理特征迥异,提示DCIS-MI是DCIS发展的新阶段,有了“质”的改变,本结论有待后续更大样本量的研究进行验证。     

A proposal for the histopathological diagnosis of ductal carcinoma in situ of the Breast

BACKGROUND: As the incidence of ductal carcinoma in situ (DCIS) is increasing, it is necessary to make a guideline for the pathological examination and diagnosis of DCIS, by creating criteria based on clinical and biological aspects of the disease. METHOD: We collected biopsy specimens originally diagnosed as benign lesions, from patients who subsequently developed invasive carcinoma in the ipsilateral breast. The histology of the biopsy specimens was re-evaluated principally according to the 1995 Philadelphia Consensus on DCIS. Histopathological agreement on each biopsy specimen was made by the JBCS Study Group members under a multiviewer microscope. In the course of making conclusive agreements among the pathologists, we developed a consensus for the histopathological diagnosis of DCIS, especially non-comedo types. RESULTS: DCIS is defined as a carcinoma of ductal epithelial origin, without any evidence of stromal invasion. It is necessary to note the methods of pathologic examination required to diagnose DCIS. Stromal invasion is an important prognostic factor, and should be diagnosed with caution. Classification of proliferative ductal lesions as benign or malignant (DCIS), the subtype of DCIS (nuclear grade, architecture, and necrosis), and the histological grading of DCIS are proposed and recommended. CONCLUSION: Although we have made a new proposal according to current concepts, there are still several unresolved problems. Thus further examination and modification will be necessary in the future.     

Differential distribution of ErbB-2 and pS2 proteins in ductal carcinomain situ of the breast

Summary We examined the expression of ErbB-2 and pS2 proteins in 59 ductal carcinomain situ (DCIS) of the breast, either pure DCIS or DCIS associated with invasive carcinoma, using immunohistochemical staining of paraffin-embedded sections. Positive staining for ErbB-2 and pS2 proteins was noted in 32% (19/59) and 46% (27/59) of DCIS, respectively. An inverse relationship between ErbB-2 and pS2 status in DCIS was observed (p < 0.01). From the viewpoint of histological subtype, the prevalence of ErbB-2 protein expression was significantly higher in the comedo subtype than the cribriform-micropapillary subtype. The prevalence of immunoreactivity for ErbB-2 in solid subtype was intermediate between those of the other two groups. In contrast, the prevalence of pS2 expression was significantly lower in the comedo subtype than in the cribriform-micropapillary subtype. Again, the prevalence of pS2 protein expression in the solid subtype was intermediate between those of the other two subtypes. Our results suggest that DCIS is biologically heterogeneous with regard to such marker substances. This has possible implications for management of these lesions.     

Axillary staging in ductal carcinoma in situ with microinvasion: A meta-analysis

IntroductionDuctal carcinoma in situ with microinvasion (DCISM); arguably a more aggressive subtype of DCIS, currently has variable recommendations governing its staging and management in the UK. As a result, there is ongoing controversy surrounding the most appropriate management of DCISM, in particular the need of axillary staging.MethodA search was conducted on the databases MEDLINE and Embase using the keywords: breast, DCISM, microinvasion, “ductal carcinoma in situ with microinvasion”, sentinel lymph node biopsy, SLNB, axillary staging was performed. 23 studies were selected for analysis. Primary outcome was the positivity of metastasis of lymph node; secondary outcome looked at characteristics of DCISM that may affect node positivity.ResultsA total of 2959 patients were included. Significant heterogeneity was observed amongst the studies with regards to metastases (I² = 61%; P < 0.01). Lymph node macrometastases was estimated to be 2%. Significant subgroup difference was not observed between SLNB technique and lymph node macrometastases (Q = 0.74; p = 0.69). Statistical significance was observed between the focality of the DCISM and lymph node macrometastases (Q = 8.71; p = 0.033).ConclusionAlthough histologically more advanced than DCIS, DCISM is not linked with higher rates of clinically significant metastasis to axillary lymph nodes. Survival rates are very similar to those seen in cases of DCIS. Current evidence suggests that axillary staging in cases of DCISM will not change their overall management, thus may only be an unnecessary and inconvenient additional intervention considering the majority of DCISM diagnoses are made from post-operative pathology samples. A multidisciplinary team approach evaluating pre-operative clinical and histological information to tailor the management specific to individual cases of DCISM would be a preferred approach than routine axillary staging.     

The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast

Aim

Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM.

Methods

A review of 51 patients with a diagnosis of DCIS (n = 45) or DCISM (n = 6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed.

Results

In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (<2 mm) only. In 2 patients, histopathology demonstrated a macrometastasis (>2 mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found.

Conclusions

In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear.     

Advances and controversies in management of breast ductal carcinoma in situ (DCIS)

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. It accounts for 25% of all breast cancers diagnosed, as a result of the expansion of breast cancer screening and is associated with a high survival rate. DCIS is particularly clinically challenging, due to its heterogeneous pathological and biological traits and its management is continually evolving towards more personalized and less aggressive therapies. This article suggests evidence-based guidelines for proper DCIS clinical management, which should be discussed within a multidisciplinary team in order to propose the most suitable approach in clinical practice, taking into account recent scientific studies.Here we include updated multidisciplinary treatment protocols and techniques in accordance with the most recent contributions published on this topic in the peer-reviewed medical literature, and we outline future perspectives.     

Immunohistochemical expression of uPA,PAI-1, cathepsin D and apoptotic cells in ductal carcinoma in situ of the breast

BACKGROUND: We examined the relationship between biological markers, apoptotic indices and pathologic subtypes of ductal carcinoma in situ (DCIS) of the breast. The tumor-biological factors can be divided into invasive and proliferative markers. We chose urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and Cathepsin D as invasive markers, and Ki-67 and C-erbB2 oncoproteins as proliferative factors for our study. METHODS: We used immunohistochemical methods to investigate the expression of uPA, PAI-1, Cathepsin D, Ki-67, C-erbB2 and ssDNA (single-stranded DNA for apoptotic cells) in 20 cases of DCIS. Tumor histological grade and the immunohistochemical expression of invasive and proliferative markers were compared. RESULTS: Histological grade is associated with C-erbB2, MIB-1, apoptotic index (AI) and expression of PAI-1 in cancer and stroma. The correlation coefficient of the MIB-1 index and AI was 0.867. Of these invasive markers, only expression of PAI-1 in tumor and in stroma was associated with C-erbB2. CONCLUSION: Our results show that the apoptosis index is closely related to the MIB-1 index, and also suggest that the immunohistochemical detection of PAI-1 in the cytoplasm of both carcinoma cells and stromal cells of DCIS is related to histological grade and expression of the proliferative markers MIB-1 and C-erbB2. Therefore, we infer that both invasiveness and proliferation are affected by the tumorigenesis of DCIS.     

Treatment of noninvasive carcinoma: Fifteen-Year results at the National Cancer Center Hospital in Tokyo

The introduction of screening mammography (MMG) will lead to increased detection of preclinical early breast cancer in Japan. It has become more important to understand the nature of these lesions. We tried to elucidate the long term prognosis and clinical and pathological characteristics of noninvasive cancers. A total of 336 (5.4%) ductal carcinoma in situ (DCIS) and 32 (0.5%) lobular carcinoma in situ (LCIS) were diagnosed in 6 277 breast carcinomas at the National Cancer Center Hospital from 1962 to 1995. Most (80%) LCIS occurred in premenopausal women. LCIS has significantly higher bilaterality than that of DCIS. Local recurrence occurred in approximately 10% of patients after breast conserving surgery for DCIS and LCIS. Four patients died of breast carcinoma, which were initially diagnosed as noninfiltrating carcinoma. The 15-year cause specific survival rates of patients with DCIS and LCIS were 98.5 % and 100 %, respectively.     

乳腺导管内癌及其微浸润癌病理和生物学指标表达差异的临床意义

目的比较乳腺导管内癌（DCIS）与微浸润癌（DCIS—MI）的病理及生物学指标表达差异,探讨DCIS发展为浸润癌的过程中可能存在的病理或生物学特性改变。方法回顾分析40例DCIS和30例DCIS-MI,采用Pearsonx。检验比较两者导管内癌成分的病理学指标,采用Wilcoxon秩和检验比较两者雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体（HER-2）、P53及Ki67生物学指标的差异。结果DCIS的病理分型中,粉刺型和非粉刺型的病例分别占25．0％（10／40）和75．0％（30／40）,而DCIS。MI的导管内癌成分中粉刺型和非粉刺型分别占63．3％（19／30）和36．7％（11／30）,两者差异有统计学意义（0=10．38,P=0．001）;DCIS—MI的导管内癌成分中高级别的核分级和伴坏死的比例明显高于DCIS（x2=9．52,P=0．009,x2=8．57,P=0．003）。DCIS与DCIS—MI两组间ER、PR、HER-2和P53的表达差异均无统计学意义（P〉0．050）。DCIS—MI中Ki67增殖指数高表达（〉20％）比例明显高于DCIS（40．0％比17．5％;Z=-2．35,P=0．019）。结论Ki67增殖指数对评价DCIS发生浸润有一定的临床价值。     

Bilateral ductal carcinoma in situ (DCIS) in a male breast: A case report

Objectives: This case is presented to emphasize the importance of recognizing nipple discharge as a clinical sign of male ductal carcinoma in situ and an opportunity for early diagnosis. Clinical presentation and intervention: A 68-years old gentleman presented with bilateral bloody nipple discharge. Clinical examination of breasts showed no masses in either breasts and no axillary lymphadenopathy. He was investigated with bilateral mammogram, ultrasound scan and magnetic resonance imaging of the breasts. All were leading to a diagnosis of intraductal papilloma on the left retroareolar region and suspicious microcalcifications on the right retroareolar area. Retroareolar excision under general anesthesia confirmed the presence of DCIS in both specimens. Completion mastectomy was performed which showed no residual disease in either breasts. Conclusion: DCIS in male breast is very rare and hard to diagnose due to male breast morphology. It is best treated with mastectomy without axillary dissection. Keywords: Ductal carcinoma in situ, DCIS, male breast cancer.