Non-invasive Component Research Articles

Utility of Cytokeratin 5/6, Cytokeratin 20, and p16 in the Diagnosis of Reactive Urothelial Atypia and Noninvasive Component of Urothelial Neoplasia

The utility of cytokeratin (CK)5/6 in distinguishing reactive urothelial atypia (RA) from urothelial carcinoma in situ (CIS) and from noninvasive component of high-grade papillary urothelial carcinoma (PUC) is unknown. Twenty RA with or without papillary hyperplasia and 90 noninvasive components of neoplastic urothelial lesions were submitted for immunostaining with CK5/6, CK20, and p16. Diffuse and strong reactivity involving the full or nearly full thickness of urothelium was observed with CK5/6 in 90% of RA cases. CK20 and p16 were negative in 90% and 85% of the RA cases, respectively. For CIS and noninvasive components of high-grade PUC without squamous differentiation, there was no CK5/6 staining or reactivity in the basal layer only. CK20 and p16 showed strong positivity in full thickness of urothelium in 75% to 85% of cases. CIS with weak/focal or negative reactivity for p16 or CK20 exhibited moderate cytologic atypia. Low-grade PUC displayed variable reactivity for CK5/6, CK20, and p16. Urothelial lesions with squamoid or basaloid features showed positive reactivity for CK5/6. Urothelial lesions with glandular differentiation showed negative reactivity for CK5/6. Diffuse CK5/6 reactivity in RA and negative CK5/6 reactivity in CIS and PUC may be helpful in distinguishing between these 2 entities.

Pathological aspects of the intraductal spread of breast cancer

The intraductal spread of breast cancer is a major cause of local recurrence following breast-conserving therapy. To properly understand this pathology, three-dimensional (3D) cancer localization within the mammary ductal-lobular system (MDLS) is necessary. To this end we generated computer-assisted 3D reconstructions of all MDLSs using 2-mm-thick serial sections of surgically resected specimens. We then analyzed the characteristics of intraductal spread of breast cancer. In our study of quadrantectomy specimens from patients with primary invasive breast carcinoma, the intraductal spread of breast cancer was found to be continuous from the invasive tumor and spreading along the mammary glandular tree. The pattern is categorized into three types: the central type, the peripheral type, and the extensive type. The central type was found to be most common. A 3D analysis of total mastectomy specimen from a patient with primary non-invasive breast carcinoma revealed regional intraductal spread extending within and filling a single MDLS. The analysis also revealed the presence of ductal anastomoses connecting adjacent MDLSs. These ductal anastomoses were found to be an anatomical risk factor for extensive intraductal spread of breast cancer across multiple MDLSs. To minimize residual non-invasive components of breast carcinoma in the conserved breast, which is strongly associated with the outcome of local control of breast-conserving therapy, it is necessary to determine the optimum surgical margins in a flexible, patient-specific manner. This determination should be based on anatomical characteristics of the MDLS, such as those identified in the present study.

Frequency of Subtypes of Biliary Intraductal Papillary Mucinous Neoplasm and Their MUC1, MUC2, and DPC4 Expression Patterns Differ from Pancreatic Intraductal Papillary Mucinous Neoplasm

Biliary intraductal papillary mucinous neoplasm (B-IPMN) has been proposed as a unique clinicopathologic disease with distinct histopathologic features, although wide acceptance remains controversial. A recent consensus conference classified pancreatic IPMN (P-IPMN) into 4 subtypes (ie, gastric, intestinal, pancreatobiliary, oncocytic) based on morphologic appearance and mucin (MUC) staining properties. The aim of this study was to determine whether B-IPMN has similar histopathologic and immunologic subtypes to P-IPMN. Specific immunostaining for MUC1, MUC2, and deleted for pancreas cancer, locus 4 were performed on specimens from 19 patients with a histopathologic diagnosis of B-IPMN. Immunostaining patterns of B-IPMN were correlated with histopathology. Based on histopathology, the following subtypes of B-IPMN were identified: pancreatobiliary n = 9 (47%), intestinal n = 8 (42%), oncocytic n = 2 (11%), and gastric n = 0 (0%). Pancreatobiliary and oncocytic subtypes of B-IPMN were positive for MUC1 and negative for MUC2, and intestinal subtypes were positive for MUC2 and negative for MUC1. Thirteen of the 19 B-IPMN were associated with invasive carcinoma; loss of deleted for pancreas cancer, locus 4 was found in 6 of 13 invasive components and in 3 of 19 noninvasive components of B-IPMN. Five-year survival for patients with resected B-IPMN and invasive carcinoma was 38%, which is similar to that for resected P-IPMN with invasive carcinoma. Histopathologic subtypes and type-specific MUC expression patterns of B-IPMN resemble those of P-IPMN. MUC1 expression and/or absence of MUC2 expression, which correlate with aggressive features of P-IPMN, were found in B-IPMN and correlate with invasive B-IPMN. Loss of deleted for pancreas cancer, locus 4 parallels the findings observed in P-IPMN. These findings provide additional support that B-IPMN is a unique entity with similarities to main duct P-IPMN.

Canine mammary mixed tumours: immunohistochemical expressions of EGFR and HER-2

Benign mixed tumours (BMTs) are frequently found in the mammary glands of female dogs, but the factors determining malignant transformation in these tumours are unknown. To evaluate the expression of the oncoproteins, human epidermal growth factor receptor 2 (HER-2) and epidermal growth factor receptor (EGFR), in 46 carcinomas in BMTs (CBMTs) and to verify their possible association with the malignancy of the tumours. Immunohistochemical expression was analysed in benign and malignant components separately, and then compared with 74 cases of BMTs. Among the CBMTs, positivity for HER-2 was found in the benign histological component of 4.3% (2/46), in the malignant epithelial non-invasive component of 14.8% (4/27) and in the malignant invasive epithelial component of 13.6% (6/44) of cases. Two of the 24 (8.3%) BMTs were positive for HER-2. There was no relationship between HER-2 and the tumour components. There was no significant difference between BMTs and CBMTs. Positivity for EGFR was found in the benign component of 17.4% (8/46) of the CBMTs, in the malignant epithelial non-invasive component of 40.7% (11/27%) and in the invasive epithelial malignant component of 45.4% (20/44). EGFR positivity was significantly associated with the invasive component of CBMTs. EGFR may contribute to malignant epithelial transformation of BMTs. In contrast, HER-2 overexpression may not be associated with the acquisition of a malignant epithelial phenotype.

Tyrosine Kinase Inhibitors and Epidermal Growth Factor Receptor (EGFR) Mutations in Non-Small Cell Lung Cancer

Tyrosine Kinase Inhibitors and Epidermal Growth Factor Receptor (EGFR) Mutations in Non-Small Cell Lung Cancer

Abstract 1417: Molecular abnormalities associated to the progression of lung adenocarcinomas with BAC features from non-invasive to invasive patterns

Abstract Background: Most invasive lung adenocarcinomas (LAC) consist of mixed histological growth patterns including a non-invasive component referred as bronchioloalveolar carcinoma (BAC). Invasive LACs with BAC features are suspected to evolve from pure non-invasive (BAC) tumors. However, in this tumor type there is limited information about the molecular abnormalities associated to the progression from non-invasive to the invasive components. Materials and methods: To perform a detailed mapping analysis of molecular abnormalities comparing non-invasive and invasive sites in lung AC with BAC features we selected archival tumor tissue specimens from 77 LACs with more than 10% of non-invasive component out of 553 available tumors. Using whole histologic sections, we analyzed on each component (non-invasive and invasive) the immunohistochemical (IHC) expression of five markers known to be deregulated in lung AC, including EGFR, Her2-Neu, TTF-1, BRG1 and p53. We also compared in both tumor components the status of EGFR gene copy number gain (CNG) by fluorescent in situ hybridization and mutation of EGFR (exon 18-21) and KRAS (codons 12 and 13) by PCR-based sequencing using DNA extracted from microdissected tissue. For EGFR, we defined 2 types of CNGs: low (trysomy and low-polysomy), and high (high-polysomy and amplification). Results: Most cases had similar levels of expression in the non-invasive and invasive components of LAC for all IHC markers: EGFR, 54/70, 77%; Her2-Neu, 56/71, 79%; p53, 58/72, 80%; TTF-1, 57/71, 80%; and BRG1, 70/73, 96%. In a subset of cases, we found that the invasive component of LAC showed higher frequency of overexpression than non-invasive sites of EGFR (invasive 14/70, 20% vs. non-invasive 2/70, 3%) and Her2Neu (13/71, 18% vs. 2/71, 3%). EGFR mutations of exons 18-21 were found in 11/44 (20%) LAC, and in 7 (64%) mutant tumors the mutations were detected only in the invasive component. KRAS mutations were found in 14/56 (25%) tumors, and in all mutant tumors the mutations were found in both the non-invasive and corresponding invasive components. Any EGFR CNG was found in the invasive component of 20/56 (36%) tumors, including 9 cases with high CNG (4 high-polysomy and 5 gene amplification). In most (16/20, 80%) tumors the invasive component demonstrated higher CNG levels than the corresponding non-invasive sites. Interestingly, all 5 invasive tumors with EGFR amplification did not show such of abnormality in the corresponding non-invasive site. Conclusions: Our findings suggest that in LAC with BAC features the overexpression of EGFR and Her2Neu, and EGFR gene abnormalities (CNGs and mutations) are associated with the progression of non-invasive to invasive components of the tumors. In contrast, in LAC with KRAS mutation this abnormality commences at the non-invasive stage of tumor development. Supported by grant from Uniting Against Lung Cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1417. doi:10.1158/1538-7445.AM2011-1417

Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget’s disease

We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.

Fascin stain as a potential marker of invasiveness in carcinomas of the urinary bladder: A retrospective study with biopsy and cytology correlation

The evaluation of invasion in urothelial carcinomas of the urinary bladder cannot be determined on cytology and can be particularly challenging in biopsy cases with limited sampling. Recent studies of bladder resection specimens suggest that fascin overexpression may be a marker of aggressive urothelial carcinomas and can help facilitate the assessment of invasion. In this study, we evaluated urine cytology and corresponding biopsy specimens with proven invasive urothelial carcinoma for fascin expression by immunohistochemistry. Thirty-five patients diagnosed with positive urine cytology and biopsy-proven invasive urothelial carcinoma between January 2003 and February 2009 were identified. We found increased fascin expression in 100% (35/35) of SurePath™ urine cytology preparations as well as 100% (35/35) of corresponding biopsy cases with invasive urothelial carcinoma. On urine cytology, cytoplasmic fascin staining was moderate to intense in malignant tumor cell clusters and single cells and not observed in benign urothelial cells. Staining in biopsy cases was generally intense and cytoplasmic and present in both the invasive (100%) and noninvasive (31%) components of the lesion. These findings uphold the association of increased fascin expression in invasive urothelial carcinomas of the urinary bladder. We furthermore demonstrate that fascin staining can be performed successfully on SurePath™ urine cytology preparations in which increased fascin expression correlates with invasion on biopsy. While not a definitive marker of invasion, as it is observed in in situ carcinoma, we conclude that the utilization of fascin immunohistochemistry on urine cytology might serve as a useful adjunct in predicting invasiveness in subsequent biopsies.

Utility of Intraoperative Frozen-Section Examinations of Surgical Margins: With Special Reference to the Implication of Features of Margin-Exposed Tumor Components on Further Surgical Treatment.

Abstract Purpose: The assessment of surgical margins is important in breast conserving surgery (BCS). In BCS, we usually resect additional specimens after the diagnosis of positive margin by intraoperative frozen-section examinations (IFE). However, we often experience the patients who received additional resections after positive results by IFE but no tumors were detected in the permanent sections. If we can predict the absence of residual tumor components from IFE, it may be possible to avoid additional mastectomy. In the present study, we tried to identify histological characteristics of margin-exposed tumor components on IFE as predictive factors for the residual tumor components in the additionally resected specimens. Methods: 1,835 cases underwent BCS between October 1999 and July 2008 at the National Cancer Center Hospital, Tokyo, Japan. By the review of the pathological database, we chose patients who had positive surgical margins determined by IFE and had undergone immediate additional resection. Two observers (MK, HT) reviewed the slides of frozen sections and confirmed the presence of tumor components. Results: 220 cases (12%) were eligible for this study. Within the specimens of additional resection, residual tumors existed in 114 cases (51.8%) and no tumors existed in 106 cases (48.2%). As characteristics of the primary tumors, invasive lobular carcinoma, pT3, EIC(+) and lymphatic invasion were significantly associated with the residual tumor components. As characteristics of margin-exposed tumor components on IFE, the number of positive margins, their maximum diameter and histological type were correlated with the residual tumors. The rate of detection of the residual tumors was significantly higher in the group with multiple positive margins (50/72, 69%) than in the group with a single positive margin (64/148, 43%) (p=0.0003). The residual tumors were detected in 36.5% (38/104), 60.8% (62/102), and 100% (14/14) of the groups with <6 mm, ≥6 to <20 mm, and ≥20 mm of the maximum diameter of the exposed tumor components, respectively (p=0.0005). Although there was no significant relationship in the rate between the group with exposed noninvasive components and that with exposed invasive components, the residual tumor components were detected more frequently in the group with exposed lobular carcinoma components (20/29, 69%) than in the group with exposed ductal carcinoma components (94/191, 49%) (p=0.047). By a multivariate analysis, the number of positive margins and the maximum diameter were independent risk factors of the residual tumors. Conclusion: The diagnosis of positive margins by IFE was useful for the prediction of residual tumors, and three histological properties of margin-exposed tumor components were correlated with the absence of residual tumor components. It may be possible to consider stratification of additional surgical therapy according to the characteristics of margin-exposed tumor components on IFE. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4118.

The use of radioisotope combined with isosulfan blue dye is not superior to radioisotope alone for the identification of sentinel lymph nodes in patients with breast cancer

Isosulfan Blue dye (BD) allergic drug reactions (ADR) occur in up to 2% of patients undergoing SLN biopsy (SLNB). We sought to determine if BD enhances the performance of SLNB such that this risk is justified. A retrospective review of 392 breast cancer patients undergoing SLNB between 8/99 and 8/04 was performed; 208 patients had radioisotope (ISO) alone, 167 had ISO+BD. Total SLN and positive SLN in each group were compared. We examined the ISO+BD group for concordance and the presence of blue only nodes. The effect of tumor location, injection site, angiolymphatic invasion, Her2/neu expression, and the presence of a noninvasive component were studied. Chi-square, linear regression, Fisher t tests, and ANOVA were performed. SLN were identified in 94% of ISO and 96% of ISO+BD patients. The mean number SLN from the ISO group was 2.01, 1.93 for ISO+BD; 27% of ISO and 21% of ISO+BD patients had positive nodes. These differences were not significant. No difference for tumor location, injection site, angiolymphatic invasion, Her2/neu expression, or the presence of a noninvasive component was found. The addition of BD to ISO in patients with invasive breast cancer does not significantly enhance the performance of SLNB.

Use of the noninvasive components of the mayo score to assess clinical response in Ulcerative Colitis

The Mayo score and a noninvasive 9-point partial Mayo score are used as outcome measures for clinical trials assessing therapy for ulcerative colitis (UC). There are limited data assessing what defines a clinically relevant change in these indices. We sought to assess what constitutes a clinically meaningful change in these indices using data from a recently completed placebo-controlled clinical trial. In all, 105 patients were enrolled in a 12-week randomized, placebo-controlled trial assessing rosiglitazone for treatment of mild to moderate UC. We compared the change in the Mayo score, the partial Mayo score, and a 6-point score composed just of the stool frequency and bleeding components of the Mayo score to the patient's perception of disease activity at week 0 and week 12. Optimal cutpoints were calculated as the maximal product of sensitivity and specificity. Each index was strongly correlated with the patient's rating of disease activity at week 12 (Spearman correlations 0.61-0.71, P < 0.0001 for all correlations). The maximal product of sensitivity and specificity to identify patient reported improvement of disease activity was achieved using cutpoints for change of 2.5 for the Mayo score (sensitivity 88%, specificity 80%), 2.5 for the partial Mayo score (sensitivity 88%, specificity 87%), and 1.5 for the 6-point score (sensitivity 88%, specificity 80%). The partial Mayo score and the 6-point score composed solely of the stool frequency and bleeding components performed as well as the full Mayo score to identify patient perceived clinical response.

Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening

The progression of ovarian carcinoma from stage I when it is confined to the ovaries and curable to disseminated abdominal disease, which is usually fatal, is poorly understood. An accurate understanding of this process is fundamental to designing, testing, and implementing an effective screening program for ovarian cancer. Pathologic features of the primary ovarian tumors in 41 FIGO stage I ovarian carcinomas were compared with those in 40 stage III carcinomas. The primary ovarian tumors in stage I cases, when compared with stage III, respectively, were significantly larger (15.4 versus 9.8 cm), were less frequently bilateral (12% versus 75%), more frequently contained a noninvasive component (88% versus 30%), had a higher proportion of a noninvasive component (42% versus 8%), and were more often nonserous (83% versus 20%) (P < 0.001 for all five comparisons). There are significant pathologic differences between the primary ovarian tumors in stage I and III ovarian carcinomas that are very difficult to explain by a simple temporal progression. These findings along with the growing body of literature suggest that early- and advanced-stage ovarian cancers are in many instances biologically different entities. This knowledge may have significant implications for our understanding of the biology of early- and advanced-stage ovarian cancer and therefore on the development of screening strategies for ovarian cancer.

FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer

FGFR3 is frequently activated by mutation in urothelial carcinoma (UC) and represents a potential target for therapy. In multiple myeloma, both over-expression and mutation of FGFR3 contribute to tumour development. To define the population of UC patients who may benefit from FGFR-targeted therapy, we assessed both mutation and receptor over-expression in primary UCs from a population of new patients. Manual or laser capture microdissection was used to isolate pure tumour cell populations. Where present, non-invasive and invasive components in the same section were microdissected. A screen of the region of the highest tumour stage in each sample yielded a mutation frequency of 42%. Mutations comprised 61 single and five double mutations, all in hotspot codons previously identified in UC. There was a significant association of mutation with low tumour grade and stage. Subsequently, non-invasive areas from the 43 tumours with both non-invasive and invasive components were analysed separately; 18 of these had mutation in at least one region, including nine with mutation in all regions examined, eight with mutation in only the non-invasive component and one with different mutations in different regions. Of the eight with mutation in only the non-invasive component, six were predicted to represent a single tumour and two showed morphological dissimilarity of fragments within the block, indicating the possible presence of distinct tumour clones. Immunohistochemistry showed over-expression of FGFR3 protein in many tumours compared to normal bladder and ureteric controls. Increased expression was associated with mutation (85% of mutant tumours showed high-level expression). Overall, 42% of tumours with no detectable mutation showed over-expression, including many muscle-invasive tumours. This may represent a non-mutant subset of tumours in which FGFR3 signalling contributes to the transformed phenotype and which may benefit from FGFR-targeted therapies.

Breast Signet-ring Cell Lobular Carcinoma Presenting with Duodenal Obstruction and Acute Pancreatitis

We report here an extremely rare case of breast signet-ring cell carcinoma (SRCC) initially manifesting as duodenal metastasis and acute pancreatitis. A 62-year-old female presented with duodenal obstruction and swollen head of the pancreas, and the diagnosis of acute pancreatitis was initially made. Upper gastrointestinal endoscopy revealed duodenal stenosis with erosive mucosa, with signet-ring cells infiltrating the submucosal layer, suggesting duodenal metastasis of SRCC. Despite absence of a palpable mass in both breasts, computed tomography revealed diffuse enhancement of the left breast in addition to left axillary lymphadenopathy. Histological examination of mammary needle biopsy samples revealed SRCC with a non-invasive lobular carcinoma component. Primary breast SRCC with duodenal metastasis was therefore diagnosed. The patient underwent palliative surgery twice for intestinal obstruction due to peritoneal dissemination. She has remained alive without bowel obstruction for 18 months while being treated with cytotoxic chemotherapies.

Therapy Insight: peripheral arterial disease and diabetes—from pathogenesis to treatment guidelines

The increased risk of atherothrombotic events present in all patients with peripheral arterial disease (PAD) is amplified with concomitant diabetes. Moreover, diabetes is associated with increased PAD severity. This Review summarizes atherothrombosis and PAD in patients with diabetes, and American College of Cardiology and American Heart Association guidelines for management of patients with PAD. Patients with PAD and diabetes require optimal limb care and aggressive cardiovascular risk reduction. An LDL cholesterol level of less than 1.8 mmol/l (<70 mg/dl) is the therapeutic goal in these patients, and this target should be pursued using an aggressive statin regimen. Fibrate therapy can also be indicated. beta-blockers and angiotensin-converting-enzyme inhibitors reduce cardiovascular events in high-risk patient populations, and these agents are recommended for use in patients with both diabetes and PAD. Blood pressure of less than 130/80 mmHg should be achieved, and glycated hemoglobin should be reduced to below 7%. Patients should also receive indefinite antiplatelet therapy with aspirin or clopidogrel. For patients with claudication, a supervised exercise program and cilostazol therapy to improve PAD symptoms and walking distance form the main noninvasive components of therapy. Revascularization can also be indicated in carefully selected patients with claudication. For patients with critical limb ischemia, diagnostic testing by a vascular specialist will determine whether revascularization or amputation is feasible.

On the possibility of detecting surfacing sperm whales at risk of collision using others' foraging clicks

Cetaceans are prone to collisions with fast vessels, and in areas of high cetacean and vessel density such as in the Canary Islands, the sperm whale (Physeter macrocephalus) is of great concern. Sperm whales are highly vocal and can be localized with passive sonar, but, when at or near the surface, they tend to stop vocalizing, i.e. when they are most at risk. Regrettably, ship-borne active solutions have proven inefficient due to the short detection range and the ships' high-speeds. Our objective in this paper is to evaluate the efficiency of an original passive sonar solution that would use vocalizing whale clicks at depth as acoustic sources to detect silent whales. This solution could be a non-invasive complementary component of a more complex passive localization whale anti-collision system. To meet this aim, a simulation tool for 3D acoustic propagation was designed in which a wideband Nx2D ray solution of the wave equation simulates a passive solution consisting of an arbitrary number of active acoustic sources, an illuminated object, and a receiver, all positioned in a three-dimensional space with arbitrary bathymetry. Both curved and straight ray solutions were implemented, the latter providing greater computational speeds at the expense of temporal and angular precision. The software recreates the resulting sound mixture of direct, reverberated and target back-scattered signals arriving at the array sensors for any array configuration, any number of sources and one target. Simulations show the application of the concept for the Canary Islands, with a detection range upper bound of the order of one kilometre.

Invasive cribriform carcinoma with extensive microcalcifications in the male breast

Invasive cribriform carcinoma (ICC) is a rare, unique type of invasive breast carcinoma that exhibits a cribriform pattern in the majority of the invasive component and is associated with an excellent prognosis. Only one male patient with ICC has been previously reported. Mammography studies often suggest that ICC contains microcalcifications, but the histological finding of extensive microcalcification has only been reported in one patient with ICC. Here we report a male patient diagnosed with ICC and exhibiting histologically confirmed extensive microcalcification is reported. The patient was a 64-year-old Japanese man in whom a breast tumor was detected during an annual check up. Mammography demonstrated a circumscribed high-density mass with microcalcifications. Breast-conserving surgery with axillary node dissection was performed. The tumor was located in the subareolar region of his left breast. The excised tumor had a maximum diameter of 1.0 cm, and no signs of invasion to extramammary tissue were observed. Histologically, the tumor cells were arranged in a cribriform pattern with invasive and non-invasive components. High-grade carcinoma or tubular carcinoma components were not observed. Extensive calcification was seen within the cribriform spaces. Immunohistological staining revealed that the cribriform spaces did not contain basement membrane material, and the tumor cells had not differentiated into basaloid cells or lactational mammary epithelium. The patient is presently free from local recurrence or metastasis 7 months after undergoing surgery.

Overexpression of human carcinoma-associated antigen in urothelial carcinoma of the bladder.

Human carcinoma-associated antigen (HCA) is a mucin protein whose level is increased in the sera of patients with a variety of carcinomas. We have previously shown that prostatic carcinoma overexpresses HCA in comparison to benign prostatic tissue. To our knowledge, expression of HCA in other tumors has not been reported previously. The current study was designed to determine if HCA is overexpressed in urothelial carcinoma (UCa) of the bladder. Forty cystectomy specimens with UCa were selected, of which 27 cases had invasive UCa, 21 cases had a noninvasive component, and 36 cases had benign urothelium. Seven cystectomy specimens with benign conditions were chosen as controls. Anti-HCA monoclonal antibody HAE3 was used for immunohistochemical staining. Results were recorded as positive (> or =5% of cells staining and staining intensity 2+ or 3+) or negative (<5% of cells staining or staining intensity <2+) and analyzed using the Fisher exact test. HAE3 staining was positive in 67% of invasive UCa, 29% of noninvasive UCa, but only 5% of benign urothelium specimens. The difference in HCA expression between benign urothelium and UCa and that between invasive and noninvasive UCa was statistically significant (P =.008). No statistically significant difference was found between low-grade and high-grade noninvasive papillary UCa (P =.06). Human carcinoma-associated antigen is selectively overexpressed in a significant number of cases of UCa of the bladder, suggesting the potential utility of monitoring the serum and/or urine levels of HCA in monitoring patients with HCA-positive UCa for recurrence or progression.

A case of invasive adenocarcinoma derived from intraductal papillary-mucinous carcinoma showing high MUC 1 expression in non-invasive component: Possible relationship between MUC 1 expression and tumor invasion

A case of invasive adenocarcinoma derived from intraductal papillary-mucinous carcinoma showing high MUC 1 expression in non-invasive component: Possible relationship between MUC 1 expression and tumor invasion

Pathological appraisal of lines of resection for bile duct carcinoma.

The aim of this study was to determine the most appropriate line of resection for extrahepatic bile duct carcinoma. A retrospective review was carried out of 253 resected specimens of extrahepatic bile duct carcinoma. Carcinomas were classified histologically as invasive or non-invasive in addition to assessment of the resection margin. Tumour was present microscopically at the resection margin in 80 (31.6 per cent) of 253 cases, with 46 showing marginal involvement by non-invasive carcinoma, 20 showing invasive carcinoma at a margin, and 14 showing both. Involvement of the resection margin by invasive carcinoma was encountered only when the margin was shorter than 10 mm, whereas non-invasive carcinoma was encountered even when the margin length reached 40 mm. The observed length of microscopic extension of invasive carcinoma beyond the macroscopically evident tumour mass was limited to 10.0 mm. Median microscopic extension of non-invasive carcinoma beyond the mass was 10 mm (75th percentile 19.5 and 14.5 mm in proximal and distal directions respectively; maximum 52 mm). Margins of 20 mm could be assured to be negative proximally in 89.0 per cent of cases and distally in 93.8 per cent. For eradication of invasive extrahepatic bile duct carcinoma, a 10-mm margin is required. However, additional removal of any non-invasive component requires a 20-mm margin. These guidelines should be followed in any operation performed with curative intent.