Intraductal Carcinoma Component Research Articles

In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer

Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.

Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology.

Intraductal carcinoma (IDC) of the salivary glands is an uncommon and enigmatic tumor, our understanding of which is rapidly evolving. Recent studies have demonstrated multiple IDC subtypes and consistent gene fusions, most frequently involving RET. Because IDC is a ductal proliferation surrounded by flattened myoepithelial cells, it was previously presumed to be analogous to breast ductal carcinoma in situ, but recent evidence has shown that the myoepithelial cells of fusion-positive IDC harbor the same genetic alterations of the ductal cells and are therefore neoplastic. In addition, there are rare reports of fusion-positive IDC with overt areas of irregular invasion lacking myoepithelial cells, but this phenomenon is not well documented or understood. This study aims to better characterize these frankly invasive carcinoma ex-IDC. All cases of frankly invasive carcinoma ex-IDC were obtained from the authors' files. Inclusion criteria included a component of concurrent or antecedent IDC and/or a fusion known to be associated with IDC. Immunohistochemistry (S100, SOX10, mammaglobin, androgen receptor, p63, p40) and molecular analysis (targeted RNA sequencing or large panel DNA next generation sequencing) was performed. Clinical follow-up was obtained from medical records. Ten cases of frankly invasive carcinoma ex-IDC were identified. The tumors occurred in 8 men and 2 women ranging from 33 to 82 years (mean, 66.3). All but one case arose in the parotid gland. In 4 cases, the IDC component was intercalated duct type. It was mixed apocrine/intercalated duct in two, and in the remaining 4 cases, no residual IDC was identified. The frankly invasive carcinomas were remarkably heterogeneous, ranging from minimally to widely invasive beyond the confines of the IDC, low-grade to high-grade, with morphologies that varied from duct-forming to those having clear cell or sarcomatoid features, to frankly apocrine. The original diagnoses for these cases were (adeno) carcinoma, not otherwise specified (n = 6), salivary duct carcinoma (n = 3), and secretory carcinoma (n = 1). All cases harbored fusions: NCOA4::RET (n = 6), TRIM33::RET (n = 2), TRIM27::RET (n = 1), and STRN::ALK (n = 1). Clinically, one tumor recurred locally, cervical lymph node metastases occurred in five patients, and distant metastasis later developed in four of these patients. Our findings highlight striking diversity in frankly invasive carcinomas that arise from fusion-positive IDC, a tumor which may serve as a precursor neoplasm like pleomorphic adenoma. These carcinomas vary in their extent of invasion, grade, histologic appearances, and clinical behavior. Importantly, in contrast to pure IDC, which is believed to be indolent, many frankly invasive cases were aggressive. Because RET and ALK fusions are targetable, it is important to recognize the broad spectrum of frankly invasive carcinomas that can arise from IDC, particularly because some cases are completely overrun or recur without any recognizable IDC component. These results suggest fusion analysis may be of clinical benefit on any salivary gland (adeno) carcinoma, not otherwise specified or salivary duct carcinoma.

Histological and immunohistochemical investigation of canine prostate carcinoma with identification of common intraductal carcinoma component.

A limited number of species, including men and dogs, spontaneously develop prostate cancer (PC). The histological and molecular relevance of canine PC as a model for the disease in men remains controversial. To address this challenge, this study aimed to assess the histomorphology and expression of basal cell, urothelial and neuroendocrine markers [p63, high molecular weight cytokeratin (HMWCK), Uroplakin 3 (UPIII), neuron‐specific enolase (NSE)] in canine PC (n = 41). Based on histomorphology, 10/41 (24%), 21/41 (51%) and 9/41 (22%) were classified as adenocarcinoma (AC), urothelial carcinoma (UC), and mixed carcinoma, respectively. Tumour inflammation was common, frequently severe [20/41 (49%)], and associated with neutering (p < .02) and urothelial differentiation (p < .02). Most (36/40, 90%) cancers contained only rare cells with basal cell marker expression or were negative. The expression of UPIII was absent or weak in the majority (33/38, 87%) of tumours, with moderate to strong staining in the remaining cases. NSE expression in PC was rare and limited to 2/14 (14%) cases. Tumour extension into benign ducts and glands was a common finding with presence in 17/39 (44%) of carcinomas with and without urothelial differentiation. In conclusion, we confirm that canine PC is characterized by absent or weak expression of basal cell and urothelial markers. Although rare, NSE expression, potentially indicating neuroendocrine differentiation, is reported for the first time in canine PCa. Intraductal carcinoma of the prostate with concurrent invasive PCa (IDCP‐inv) is a frequent, not previously described, finding in dogs with PC.

Exosomes exist in nipple discharge of breast cancer.

Exosomes exist in nipple discharge of breast cancer.

Elastin and collagen IV double staining: A refined method to detect blood vessel invasion in breast cancer.

Blood vessel invasion (BVI) is a prognostic indicator in various cancers. Elastic stain, which highlights blood vessel walls, is commonly used to detect BVI. In the breast, however, its diagnostic usefulness is limited because it also highlights some intraductal carcinoma components, which often mimic BVI. In this study, we aimed to improve BVI detection in breast cancer and developed a double staining: Victoria blue for elastin and immunohistochemistry for collagen IV. Collagen IV fibers were retained along the basement membranes of intraductal carcinoma components, whereas they were rearranged or lost in BVI. From these observations, we defined BVI as the presence of tumor cells inside an elastic ring with a rearrangement or loss of collagen IV fibers. Using these criteria, we found BVI in 148 cases (49%) among 304 cases of primary operable invasive breast carcinoma, and the presence of BVI correlated significantly with poor prognosis. By contrast, we detected BVI in 94 cases (31%) or 14 cases (5%) by elastic van Gieson or CD31 immunostaining among the same cases, respectively, with no statistically significant association with prognosis. Thus, elastin and collagen IV double staining facilitates the detection of BVI in breast cancer and is useful to predict prognosis.

Pathological complete response (pCR) with or without the residual intraductal carcinoma component following preoperative treatment for pancreatic cancer: Revisiting the definition of "pCR" from the prognostic standpoint.

Background and AimThere are no previous reports describing the prognostic significance of the residual intraductal carcinoma component (carcinoma in situ [CIS]) following preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to investigate the prognostic significance of a minimal residual CIS in cases with complete absence of an invasive component after preoperative treatment for PDAC.MethodsEighty‐one of 594 PDAC patients with preoperative treatment and subsequent surgery in our institute showed remarkable remission in the invasive component, which included 48 patients with the minimal residual invasive component (Min‐inv group) and 33 with absence of an invasive component (No‐inv group). We assessed the survival of these patients in association with the presence or absence of an invasive component and intraductal CIS.ResultsFive‐year overall survival in the No‐inv group patients was significantly better than that of the Min‐inv group patients (82%/66%, P = .041). Among the 33 patients in the No‐inv group, residual CIS was observed in 16 patients (CIS‐positive group), and the remaining 17 patients had no residual CIS (CIS‐negative group). There was no significant difference in survival between patients in the CIS‐positive and CIS‐negative groups (92%/78%, P = .31).ConclusionsResidual CIS in the absence of an invasive component after preoperative treatment does not yield a prognostic impact after receiving perioperative treatment for PDAC. It might be reasonable to define pathological complete response (pCR) from the prognostic standpoint as follows: pCR is the complete absence of an invasive carcinoma component regardless of residual CIS.

Dynamic contrast-enhanced and diffusion-weighted MRI of invasive breast cancer for the prediction of sentinel lymph node status.

Although sentinel lymph node biopsy (SLNB) is the current standard for identifying lymph metastasis in breast cancer patients, there are complications of SLNB. To evaluate preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) of invasive breast cancer for predicting sentinel lymph node metastasis. Retrospective. In all, 309 patients who underwent clinically node-negative invasive breast cancer surgery FIELD STRENGTH/SEQUENCE: 3.0T, DCE-MRI, DWI. We collected clinicopathologic variables (age, histologic and nuclear grade, extensive intraductal carcinoma component, lymphovascular invasion, and immunohistochemical profiles) and preoperative MRI features (tumor size, background parenchymal enhancement, internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, quantitative kinetic parameters, tumoral apparent diffusion coefficient [ADC], peritumoral maximal ADC, and peritumoral-tumoral ADC ratio). Multivariate logistic regressions were performed to determine independent variables associated with SLN metastasis, and the area under the receiver operating characteristic curve (AUC) was analyzed for those variables. 41 (13.3%) of the patients showed SLN metastasis. With MRI, tumor size (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06-1.17), heterogeneous (OR, 5.33; 95% CI, 1.71-16.58), and rim (OR, 15.54; 95% CI, 2.12-113.72) enhancement and peritumoral-tumoral ADC ratio (OR, 72.79; 95% CI, 7.15-740.82) were independently associated with SLN metastasis. Clinicopathologic variables independently associated with SLN metastasis included age (OR, 0.96; 95% CI, 0.92-0.99) and CD31 (OR, 2.90; 95% CI, 1.04-8.92). The area under the curve (AUC) of MRI features (0.80; 95% CI, 0.73-0.87) was significantly higher than for clinicopathologic variables (0.68; 95% CI, 0.60-0.77; P = 0.048) and was barely below statistical significance for combined MRI features with clinicopathologic variables (0.84; 95% CI 0.78-0.90, P = 0.057). Preoperative internal enhancement on DCE-MRI and peritumoral-tumoral ADC ratio on DWI might be useful for predicting SLN metastasis in patients with invasive breast cancer. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:615-626.

Dynamic contrast-enhanced breast magnetic resonance imaging for the prediction of early and late recurrences in breast cancer.

The aim of the study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) features for the prediction of early and late recurrences in patients with breast cancer.Of 1030 breast cancer patients who underwent surgery at our hospital from January 2007 to July 2011, 83 recurrent breast cancer patients were enrolled in this study. We compared MRI features (background parenchymal enhancement [BPE], internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, and quantitative kinetic parameters) and clinico-pathologic variables (age, stage, histologic grade, nuclear grade, existence of lymphovascular invasion and extensive intraductal carcinoma component, and immunohistochemical profiles) between patients with early (≤2.5 years after surgery) and late recurrence (>2.5 years after surgery). Cox proportional hazard regression analysis was performed to evaluate independent risk factors for early and late recurrence.On breast MRI, prominent ipsilateral whole-breast vascularity was independently associated with early recurrence (hazard ratio [HR], 2.86; 95% confidence intervals [CI], 1.39–5.88) and moderate or marked BPE (HR, 2.08; 95% CI, 1.04–4.18) and rim enhancement (HR, 2.14; 95% CI, 1.00–4.59) were independently associated with late recurrence. Clinico-pathologic variables independently associated with early recurrence included negative estrogen receptor (HR, 0.53; 95% CI, 0.29–0.96), whereas T2 stage (HR, 2.08; 95% CI, 1.04–4.16) and nuclear grade III (HR, 2.54; 95% CI, 1.29–4.98) were associated with late recurrence.In DCE-MRI, prominent ipsilateral whole-breast vascularity, moderate or marked BPE, and rim enhancement could be useful for predicting recurrence timing in patients with breast cancer.

Histopathological Study on Conservatively Operated Breast Carcinomas.

In this histopathological study we looked at 303 cases of breast carcinomas, managed though conservative breast surgery and later analysed with the help of a classical histopathological technique, paraffin embedding. The carcinomas were assessed in terms of tumor size, lymph node status, histological type, correlation between invasive tumors and an situ carcinoma component, resection margins, grading and patients age. Following assessment, we looked at associations between above morphological and clinical parameters and ipsilateral local recurrences. We concluded that more than half of our cases were carcinomas, measuring between 2 cm and 5 cm, with no associated lymph node involvement, in keeping with pTNM criteria for stage II. By far, in our study, the most frequent histopathological type was type NOS (63.37%) followed by invasive lobular carcinoma (10.56%) and mixed ducto-lobular invasive carcinoma (6.27%). Other types of invasive carcinoma were rarer, each representing less than 4% of cases. In regards to in situ carcinomas we noted the most common histological types to be both cribriform intraductal carcinoma and comedocarcinoma, each identified in 1.65% of cases. Amongst invasive breast carcinomas, infiltrating ductal carcinoma not otherwise specified (NOS) was found to be most commonly associated with in situ ductal carcinoma lesions. This was seen in 34.9% of cases, and was the only type associated with an extensive in situ component. Analysing the grading of mammary carcinomas in our study showed that the vast majority of cases (63.04%) were grade 3 tumors. In regards to surgical resection margins, ¾ of cases were noted to have negative margins. Tumor recurrences were noted in 12 cases. These cases were most commonly noted to reoccur following initial poorly differentiated, infiltrating ductal carcinomas, not otherwise specified (NOS), with positive resection margins, measuring less than 2 cm. Patiens tended to be under the age of 40 and had positive lymph nodes. The emergence of local recurrences after conservative surgery for early breast cancer is singnificantly linked to poorly differentiated primary tumors (p <0.05) but not correlated with histological type, presence of extensive intraductal carcinoma component, size of primary breast tumor or lymph node status ( p> 0.05). In terms of increasing the risk of ipsilateral recurrence the most important aspect highlighted in our sudy was the status of the resection margins. Patients with positive resection margins had a significantly high risk to develop recurrences after the conservative surgery, compared to those with negative margins (p <0.001).

Clinicopathological Features and Prognosis of Pregnancy Associated Breast Cancer – A Matched Case Control Study

Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women ≤45 years, diagnosed in the 2nd Department of Pathology, Semmelweis University, Budapest, Hungary between 1998 and 2012. Histopathology information on tumor type, grade, size, T, N, lympho-vascular invasion (LVI), Nottingham Prognostic Index (NPI), associated in situ lesions and IHC charcteristics: ER, PgR, HER2, Ki67, p53 were recorded, IHC-based subtype was assessed, clinical, management and outcome data were analysed. Thirty-one breast cancer cases were pregnancy related. Clinical management data did not differ in cases and controls. Histopathology of disease at presentation was not significantly different, but NPI assessed the PABC group as having poor, whereas controls as having intermediate prognosis. Associated in situ lesion was more often high grade Extensive Intraductal Carcinoma Component (EIC) in PABC. Triple negative and LuminalB prol tumors predominated in PABC. Disease-free and overall survival was inferior compared to controls. PABC patients with LuminalB prol and Triple negative tumors had inferior outcomes. On multivariate analysis inferior prognosis of PABC was associated with pregnancy. Our study has demonstrated inferior outcome of PABC. Difference in tumor biology is reflected by the predominance of triple negative and LuminalB tumors in PABC. The strength of the study is the analysis of complete pathology and IHC data.

Influence of the in situ component in 389 infiltrating ductal breast carcinomas

Our aim was to evaluate and compare lymph node involvement, as well as disease-free survival (DFS) and overall survival (OS), between infiltrating ductal carcinoma with (group 1) and without (group 2) intraductal carcinoma component in order to determine the prognostic value of the intraductal component. Data from 389 cases of infiltrating ductal carcinoma of the breast were included in the study by means of reviewing medical charts and pathology slides. There was no statistically significant difference between both groups regarding node status. The 5-year DFS rate was 90.7% in group 1 and 81.8% in group 2 (p=0.014), with a median follow-up of 73.2months (95% CI 68.3-77.4). There was no statistically significant difference in 5-year OS between groups (98% group 1 vs. 93% group 2) with a median global survival of 134months (95% CI 131-137). The presence of intraductal component in the infiltrating carcinoma seems to increase DFS and may be an independent and favorable prognostic factor for breast cancer.

The Risk Factors Influencing between the Early and Late Recurrence in Systemic Recurrent Breast Cancer

PurposePatients with recurrent breast cancer usually die of their disease, even after radical surgery and adjuvant therapies which could reduce the odds of dying. Many studies analyzed and compared patients who died of recurrent disease with those that died without recurrent disease. However, less attention has been paid to evaluating factors associated with the timing of recurrence. Thus, the objective of this study is to investigate the correlation between various factors and the timing of recurrence.MethodsWe retrospectively reviewed the data of 95 recurrent breast cancer patients who underwent curative surgery to determine the prognostic factors such as menopausal status, operation method, stage, nodal status, histologic grade, nuclear grade, extensive intraductal carcinoma component, hormone receptor, p53, c-erbB-2, Ki-67, and molecular subtype. We had attempted to compare the recurrent patients within 2 years after operation and adjuvant chemotherapies as the early recurrence with those over 2 years as the late recurrence.ResultsHistologic grade (p=0.005), nuclear grade (p<0.001), p53 (p=0.022), and Ki-67 (p<0.001) were significant different factors that influenced the systemic recurrence between early recurrence and late recurrence. In stage I/II, histologic grade (p=0.001), nuclear grade (p<0.001), and Ki-67 (p=0.005) were significant factors that influenced the systemic early recurrence. In stage III, nuclear grade (p=0.024), and Ki-67 (p=0.001) were significant factors that influenced the systemic early recurrence. But subtypes (p=0.189, p=0.132, p=0.593, p=0.083) are not associated with the timing of recur rence.ConclusionIn systemic recurrent breast cancer patients, the risk factors such as histologic grade, nuclear grade, p53 and Ki-67 are also associated with the timing of recurrence. We sug gest that these patients should be proper treated and be closely followed up.

Primary mammary mucinous cystadenocarcinoma: Cytological and histological findings

Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation.

Intraductal carcinoma component as a favorable prognostic factor in biliary tract carcinoma

The aim of this study is to evaluate the prognostic impact of an intraductal carcinoma component and bile duct resection margin status in patients with biliary tract carcinoma. An intraductal carcinoma component was defined as carcinoma within the bile duct outside the main tumor nodule consisting of a subepithelial invasive component. Surgically resected materials from 214 patients were evaluated by histological observations. Seventy-nine patients (36.9%) with an intraductal carcinoma component infrequently developed large tumors and infrequently showed deep invasion and venous, lymphatic and perineural involvement in the main tumor nodule. An intraductal carcinoma component was inversely correlated with advanced clinical stage, and was shown to be a significantly favorable prognostic factor by both univariate and multivariate analyses. Proximal (hepatic) side bile duct resection margin status was categorized into negative for tumor cells, positive with only an intraductal carcinoma component [R1 (is)], and positive with a subepithelial invasive component (R1). Forty-five patients (21.0%) with an R1 resection margin had a poorer prognosis than 148 patients (69.2%) with a negative resection margin, whereas 21 patients (9.8%) with an R1 (is) resection margin did not. In patients with an R1 resection margin, the risk of anastomotic recurrence was higher, and the period until anastomotic recurrence was shorter, than in patients with an R1 (is) resection margin. Surgeons should not be persistent in trying to achieve a negative surgical margin when the intraoperative frozen section diagnosis is R1 (is), and can choose a safe surgical procedure to avoid postoperative complications.

Ductal Carcinoma In Situ Arising in a Benign Phyllodes Tumor: Report of a Case

Malignant epithelial change within a phyllodes tumor (PT) is a rare event. To our knowledge, only six cases of ductal carcinoma in situ arising in a PT have been reported in English. We report a case of PT with an intraductal carcinoma component, which grew rapidly to a huge size in 3 months. Histologically, the stromal element showed mild to moderate cellularity with few mitoses and mild nuclear atypia. The epithelial element consisted of irregularly dilated ducts with a phyllodes structure that had moderate to severe epithelial hyperplasia, and foci of cribriform ductal carcinoma in situ with comedo necrosis.

Primitive neuroectodermal tumor of the breast: Immunohistochemistry and fluorescence in situ hybridization

A case of primitive neuroectodermal tumor (PNET) that developed as a breast lump in a 47-year-old Japanese woman is reported. After fine-needle aspiration (FNA) cytology, a mastectomy was performed. The surgical specimen was a well-circumscribed tumor, 21 x 18 x 18 mm, localized in the breast. The tumor cells were small and round with scant cytoplasm, and proliferated in sheets or solid nests. No intraductal carcinoma component was present. The tumor cells were immunohistochemically positive for neural cell adhesion molecule (CD56), neuron-specific enolase and synaptophysin, and they showed membranous immunoreactivity for the MIC2 protein (CD99). Fluorescence in situ hybridization (FISH) indicated a rearrangement of the EWS region on chromosome 22, which is highly specific for Ewing's sarcoma and PNET, which are referred to as the Ewing's sarcoma family of tumors (EFT). No other lesions suggestive of the primary site of this tumor, such as bone, soft tissue, or other organs were detected. The patient has been disease free for 6 months after surgery followed by chemoradiation therapy. FISH is extremely useful for accurate diagnosis of EFT, especially in cases of unusual locations.

Invasive ductal adenocarcinoma of the pancreas may originate from the larger pancreatic duct: a study of 13 tumors less than 2 cm in diameter

We aimed to elucidate the origin/primary site of invasive ductal adenocarcinoma of the pancreas, based on the distribution of intraductal carcinoma components. These components were identified by a mural elastic fiber cuff. Thirteen specimens from patients with invasive ductal adenocarcinoma (microscopically, less than 2 cm in diameter) of the pancreas were studied histopathologically. Variants of invasive ductal adenocarcinoma and intraductal papillary-mucinous carcinoma were excluded. Intraductal carcinoma components of invasive ductal adenocarcinoma were found in 12 of the specimens 13 (92%), and were observed within the tumor mass and/or on its boundary, or outside the tumor mass. Intraductal components were characterized by low papillary projections lacking a fibrovascular core, with/without surrounding tubular structures, or by irregular stratification and pleomorphism of the epithelial cells. Invasive components mostly showed a tubular pattern with desmoplasia. The distribution of the intraductal components in the 12 specimens was as follows: in 9 (75%), they were in both the main pancreatic duct and large branch ducts; and in 3, they were in the smaller branch ducts only. Invasive ductal adenocarcinomas of the pancreas may originate most frequently from the main pancreatic duct or larger branch ducts, while the smaller ducts are less often the site of cancer origin.

Histopathological study of invasive ductal carcinoma (IDC) of the pancreas without associated cancerous occlusion of the main pancreatic duct

[corrected] Invasive ductal carcinoma (IDC) of the pancreas may be associated with cancerous occlusion of the main pancreatic duct (MPD) in its growth process, but at quite low a frequency; there are patients who do not develop this occlusion. This study examined the histological features of surgical specimens from 8 patients with IDC without MPD occlusion, in comparison to 32 patients with IDC with this occlusion (controls). The pancreatic duct was identified by confirming the presence of mural elastic fibers on the wall of the pancreatic duct. Immunohistochemical staining was done with Ki-67 antibody. The frequency of IDC without MPD occlusion was very low (5.0% [2/40] patients at Kurume University and 3.1% [4/126] patients at Juntendo University). The number of intraductal carcinoma components was 1.5 +/- 1.1 per specimen in the IDCs without occlusion and 5.9 +/- 2.4 in the controls (P < 0.001). The Ki-67 labeling index was 18.0 +/- 11.7% in the IDCs without occlusion and 30.0 +/- 12.1% in the controls (P < 0.05). The number of intraductal carcinoma components and the Ki-67 labeling index were significantly lower in the IDCs without occlusion than in the controls. Our findings suggested that these two types of IDC could have different biological features.

Vascular endothelial growth factor mRNA levels quantified by reverse transcription-polymerase chain reaction in microdissected breast carcinoma tissues are correlated with histological type and grade of both invasive and intraductal components

In breast cancer, vascular endothelial growth factor (VEGF) is a prognostic factor, but the relationship of VEGF mRNA levels with various parameters or tumor progression is unclear. VEGF mRNA levels were measured in 48 cases of invasive ductal carcinoma by using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean VEGF mRNA levels were compared among different histological types and grades in 41 and 29 samples of invasive and intraductal components, respectively. VEGF mRNA levels were always higher in cancerous cells than in non-cancerous cells, but mean VEGF mRNA levels were not significantly different between invasive component (3.24 +/- 3.18-fold the value of non-cancerous tissue) and intraductal component (4.14 +/- 4.43-fold). They were higher in papillotubular type than in other types, and higher in grade 2 carcinomas than in grade 3 carcinomas of invasive component, and higher in comedo type than in other types of intraductal component. Mean VEGF mRNA levels were higher in the VEGF-immunopositive group than in the VEGF-immunonegative group. There was no correlation between VEGF mRNA levels and tumor size, nodal status, or hormone receptor status. VEGF expression may play an important role in the development of both invasive and intraductal carcinoma components, especially those carcinoma components of less aggressive histological features.

Biologically different subgroups of invasive ductal carcinoma of the pancreas: Dpc4 status according to the ratio of intraductal carcinoma components.

Among invasive ductal carcinomas of the pancreas (IDCP), there is a morphologically characteristic subgroup accompanied by abundant intraductal carcinoma components (ICCs). With the aim of determining whether ICC-rich IDCP are biologically different from ICC-poor IDCP, the expression status of Dpc4 protein was analyzed. A total of 43 IDCP was subdivided into two groups: (a). ICC-rich IDCP (ICCs area occupies >or=10% of the entire tumorous area); and (b). ICC-poor IDCP (with <10% of ICCs area). A total of 10 invasive carcinomas derived from intraductal papillary-mucinous neoplasms (ICs from IPMNs) were also analyzed. Each invasive and intraductal carcinoma area was then evaluated for Dpc4 protein status by immunohistochemistry. In a total of 43 IDCP, there were 23 ICC-rich IDCP and 20 ICC-poor IDCP. Dpc4-positive immunostaining was observed in the invasive carcinoma component of ICC-rich IDCP, ICC-poor IDCP, and ICs from IPMN in 18 of 23 (78%), 4 of 20 (20%), and 7 of 10 (70%) cases, respectively. In the intraductal component, positive staining for Dpc4 was found in 20 of 23 (87%), 3 of 7 (41%), and 8 of 10 (80%) cases, respectively. Dpc4 expression was found in both the invasive and ICC components of ICC-rich IDCP, similar to that found in IC derived from IPMN, whereas the expression of Dpc4 was largely diminished in ICC-poor IDCP. Morphologically distinct subgroups of invasive ductal carcinomas of the pancreas, namely ICC-rich IDCP and ICC-poor IDCP, are also biologically distinguishable as revealed by the differential expression of Dpc4.