Hemangioblastoma (HB) is a benign central nervous system (CNS) tumor associated with mutations in the von Hippel-Lindau (VHL) gene. Although rare outside the CNS, the pathological and genetic features remain poorly understood. We analyzed four renal hemangioblastomas (RHB). Demographics, clinical presentation, and follow-up data were collected. After assessing hematoxylin and eosin-stained slides, immunophenotyping was conducted using CA9, α-inhibin, AE1/AE3, CD10, CD56, PAX8, S100, MelanA, HMB45, CD117, FH, SDHB, and brachyury antibodies, alongside mismatch repair (MMR) deficiency examination. Additionally, whole-exome sequencing (WES) was performed in 3 tumors. Our cohort comprised 3 male and 1 female patients, with a median age of 49 years. No data on VHL disease were available. Well-circumscribed tumors (median size: 25.5 mm) displayed clear vacuolated cytoplasm with a vascular component. Immunostaining revealed expression of PAX8, α-inhibin, AE1/AE3, S100, and cytoplasmic brachyury. WES analysis detected no pathogenic mutations. No cancer-related deaths or progressions were observed. Histologically, RHB resembles low-grade ccRCC and shares expression of PAX8, pancytokeratin, and CA9. However, RHB is uniquely positive for α-inhibin, S100, and lacks VHL alterations. Its favorable prognosis underscores the importance of distinguishing it from ccRCC to prevent unnecessary treatments. Further research is warranted to elucidate the underlying genetic mechanisms.
Low-grade oncocytic tumor (LOT) of the kidney is a recently recognized renal neoplasm with distinctive morphologic, immunophenotypic, and molecular features that distinguish it from other eosinophilic tumors such as oncocytoma and chromophobe renal cell carcinoma (chRCC). This study presents a comprehensive analysis of 20 LOTs from 19 patients, integrating clinicopathological, immunohistochemical, and genetic data. LOTs typically appeared as small, unilateral, well-circumscribed tumors with a tan-brown cut surface, composed of uniform eosinophilic cells with round nuclei and occasional perinuclear halos. Key histological hallmarks included an extensive capillary network and central edematous areas without necrosis or significant atypia. Immunohistochemically, all tumors showed strong diffuse CK7 positivity and CD117 negativity, with universal expression of GATA3, GPNMB, and L1CAM. Whole-exome and panel-based sequencing revealed recurrent mutations in the mTOR signaling pathway, including MTOR, TSC1, and ATM genes. mTORC1 activation was confirmed immunohistochemically in one case. No evidence of aggressive behavior or metastasis was observed during the follow-up period (median: 4.5 years). Comparative analysis demonstrated that LOT patients were diagnosed at an older age than those with chRCC and had smaller tumors overall. This study reinforces the notion that LOT is a distinct renal tumor entity with consistent morphology, immunoprofile, and mTOR-pathway-related genetic alterations. Despite overlapping features with other eosinophilic renal neoplasms, the specific immunohistochemical profile and indolent clinical course support LOT’s classification as a unique diagnostic category.
Background Follicular dendritic cell sarcoma (FDCS) is a rare low-grade tumor of the lymph nodes, but roughly one-third of the cases emerge from extranodal sites, posing diagnostic challenges. Case presentation In this report, we present the case of a 59-year-old lady who complained of renal colic. During investigation, a kidney tumor was discovered. A radical nephrectomy was performed, and histological examination identified the tumor as a sarcomatoid renal cell carcinoma. The case was then referred to a genitourinary pathologist for further evaluation. The tumor cells exhibited positive staining for CD21, CD23, somatostatin receptor 2 A, and MDM2 expression. Additionally, MDM2 gene amplification was confirmed by the FISH study. Ultimately, the tumor was diagnosed as a primary renal FDCS. The patient was placed under active oncological surveillance and did not receive any further therapy. Remarkably, after 91 months of follow-up, she remains tumor-free. Conclusion This case represents a well-documented primary renal FDCS. Our aim in presenting this extremely rare tumor is to enhance awareness and highlight the importance of considering FDCS in the differential diagnosis.
Prostate cancer stands as the most prevalent malignant tumor among men; with its incidence increasing with advancing age. The spectrum of patient care options for this disease is broad, encompassing approaches such as "active surveillance," definitive radiation therapy, robot-assisted surgery, among others. These diverse modalities afford opportunities for cure or successful management in the majority of cases. It is paramount to underscore that optimal treatment hinges upon a multidisciplinary framework, wherein the coordinated efforts of allied healthcare professionals yield the highest standard of patient care. Hence, it is imperative for pathologists to keep abreast of contemporary processing and specimen collection protocols, as well as the potential necessity of supplementary investigations and their clinical significance. The latest Hungarian guideline on prostate cancer care features a dedicated chapter delineating the pivotal role and responsibilities of pathologists. Through this discourse, we aim to consolidate and disseminate pertinent insights, thereby fostering the continuing enhancement of pathologists' knowledge and elucidating the intricacies of histological processing to our clinical counterparts.
Background: Liver metastases (LM) are ultimately present in ~50% of all patients with metastatic breast cancer (BC). Metastatic seeding to the liver relies on the interaction between cancer cells and the host microenvironment, resulting into two main histopathological growth patterns (HGPs): the replacement HGP (metastasis mimics the liver architecture and exploits liver vasculature) and the desmoplastic HGP (presence of a fibrotic rim separating the hepatocytes from the tumor cells). While the prognostic value of these HGPs is established for colorectal cancer, with the desmoplastic HGP being associated with better prognosis, investigation is needed for BC. It has also been reported that patients with LM have a poorer response to immune checkpoints inhibitors. A systematic evaluation of the HGP and LM-associated immune infiltrates (stromal tumor infiltrating lymphocytes, sTIL) is currently lacking. In this study, we aimed at: (i) investigating HGPs and sTIL in LM from patients with BC, and, (ii) evaluating the association of these HGPs and sTIL with standard variables and outcome. Patients and methods: The study currently includes clinical data and samples from: 1) a retrospective cohort of 122 patients from 7 hospitals with surgically resected LMs (represented by 548 hematoxylin and eosin (H&E)-sections), further referred to as ‘surgical cohort’ and, 2) LMs from 2 institutional post-mortem tissue donation studies for a total of 23 patients (97 H&E-sections). All available H&E-sections were used to assess HGP and sTIL. HGPs were scored according to a standardized method (PMIDs: 35650276) and categorized per patient as pure-replacement (rHGP, i.e. 100% of the tumor-liver interface is replacement) or any-desmoplastic (dHGP, i.e. at least 1% of the tumor-liver interface is desmoplastic). sTIL are expressed as the percentage of stromal area covered by mononuclear immune cells at the metastasis-liver interface. Associations were assessed using Fisher exact and Wilcoxon tests. Univariable and multivariable Cox regression analyses stratified by center were used to evaluate the role of HGP on progression-free (PFS) and overall survival (OS). Results: In the surgical cohort, 54 (44%) of patients displayed a rHGP and 68 (56%) a dHGP. Intra-patient, meaning inter-slide, heterogeneity of the HGP was observed in 24/122 (20%) of the patients suggesting that scoring multiple slides is needed for accurate assessment of the HGPs. We did not find any statistically significant association between HGP and clinico-pathological data. Higher sTIL were associated with dHGP (p=.003), as well as with a higher histological grade (p= .087), estrogen receptor-positivity (p=0.062) and ductal histology (p= .08) of the primary tumor. rHGP was associated with worse PFS and OS, both at the univariable and multivariable level (Table). In the post-mortem cohort, we observed a higher frequency of rHGP patients (19/23 patients, 83 %) and significantly lower levels of sTIL in the rHGP patients as compared to the rHGP patients from the surgical cohort (p= .009). Conclusion: This study represents the largest study evaluating HGPs and immune infiltrates of LMs from patients with BC. Approximately half of the surgically resected LMs have a dHGP, which is associated with higher sTIL and a better prognosis. The results from the LMs from the post-mortem cohort suggest that a more advanced stage of the disease is associated with an increase in rHGP and with a more immunosuppressed environment. Table 1: Univariable and multivariable analyses Citation Format: Sophia Leduc, Maxim De Schepper, Peter Vermeulen, Giuseppe Floris, Elia Biganzoli, Vincent Donckier, Ali Bohlok, Marco Gerling, François Richard, Marion Maetens, Joris Jaekers, Baki Topal, Emily Latacz, Karen Van Baelen, Tatjana Geukens, Ha Linh Nguyen, Luc Dirix, Denis Larsimont, Sophie Van Kerckhove, Rui Caetano Oliveira, Janina Kulka, Valerio Lucidi, Yannick Meyer, Cornelis Verhoef, Eva Santos, Ferenc Salamon, Lilla Madaras, A. Marcell Szasz, Székely Borbála, Kristòf Dede, Jennie Engstrand, Carlos Fernandez Moro, Christine Desmedt. Histopathological and immune characterization of liver metastases from patients with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-06.
Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM ( n = 133 patients, 568 H&E sections) and post-mortem derived BCLM ( n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement (‘pure r-HGP’) or any-desmoplastic (‘any d-HGP’). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of ‘any d-HGP’ (56%) in the surgical samples and a higher prevalence of ‘pure r-HGP’ (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor ( p value = 0.049) and the systemic preoperative treatment before liver surgery ( p value = .039). TIL is less prevalent in ‘pure r-HGP’ as compared to ‘any d-HGP’ ( p value = 0.001). ‘Pure r-HGP’ predicts worse PFS (HR: 2.65; CI: (1.45–4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29–7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a ‘pure r-HGP’ is associated with less TIL and with the worse outcome when compared with BCLM with ‘any d-HGP’. These findings suggest that HGP could be considered to refine treatment approaches.
Bevezetés: Az intraduktális prosztatakarcinóma (IDC-P) egy ritkán előforduló szövettani entitás, amelynek jellemzője a prosztatikus daganatos sejtek duktuszokon/acinuszokon belüli terjedése. Az IDC-P hisztomorfológiai kategóriája klinikopatológiai szempontból két különálló elváltozást jelenthet: az invazív karcinómával asszociált IDC-P-t, valamint a ritkábban előforduló izolált IDC-P-t, amely a prosztata adenokarcinóma prekurzorának tartható. Szövettani differenciáldiagnózisa komoly kihívást jelent, az atípusos kribriform léziók közül az egyik legfontosabb a magas grádusú prosztata intraepithelialis neopláziától (HGPIN) való elkülönítése. Az intraduktális prosztatakarcinóma jelenléte rendszerint magas Gleason-értékű invazív karcinómával, nagy tumortömeggel, és hátrányos prognosztikus paraméterekkel társul. Esetismertetés: Esetünkben páciensünk prosztata-tűbiopsziás mintájának szövettani vizsgálata során izolált intraduktális prosztatakarcinómát észleltünk. Az eredmény ismeretében rebiopszia végzése mellett döntöttünk. Következtetések: A prosztata atípusos kribriform elváltozásainak megfelelő szövettani differenciáldiagnosztikája fokozott klinikai jelentőséggel társul, tekintettel arra, hogy a különböző entitások eltérő terápiás és prognosztikus következményekkel járnak. Mindazonáltal nincs egyértelmű konszenzus, hogy a prosztata-tűbiopsziás mintában jelenlévő izolált IDC-P rebiopsziát, vagy azonnali radikális kezelést igényel-e. Mivel azonban az izolált IDC-P csak extrém raritásként fordult elő a vizsgálatokban, és az invazív prosztatakarcinómával való társulás valószínűsége meglehetősen nagy, abban egyetértés mutatkozik a szerzők között, hogy az intraduktális karcinóma egyedüli megjelenése a tűbiopsziás mintában minimálisan igen szoros obszervációt igényel. A jövőbeli nagyobb prospektív vizsgálatok sokkal pontosabb képet nyújthatnak az IDC-P incidenciájáról, és segíthetnek meghatározni az IDC-P biopsziás mintában való jelenlétének független prediktív értékét, ezáltal segítséget nyújthatnak ezen betegek kezelésében, a klinikai döntéshozatal irányításában.
Prostatic adenocarcinoma is the most common cancer affecting men. A substantial majority of patients have the diagnosis made on fine needle biopsies. Treatment choices ranging from surveillance to radical prostatectomy or radiation therapy are largely driven by the pathologic findings in the biopsy specimen. Our review focuses on important morphologic parameters in needle biopsy and radical prostatectomy specimens. This includes Gleason score, Gleason grade, tumor quantification as well as other parameters such as extraprostatic extension, seminal vesicle invasion, perineural invasion, lymphovascular invasion. Surgical margin status and lymph node status are also discussed. Our aim was to present the most recent international guidelines of reporting of prostate adenocarcinoma.
The technique and clinical results of liver surgery are constantly evolving in recent years, and this development felt most intensely in the field of laparoscopic liver surgery. Based on the results of comparative studies reported to date, laparoscopic surgery is not inferior to open surgery. Although a very small percentage of liver resections are performed with laparoscopic technique, clearly it has a role in oncological surgery. The minor, major, anatomical, or even multi-stage liver resections can be performed with laparoscopy. The previously general recommendation, that lesions in the front segments of the liver are recommended for the minimally invasive technique is currently outdated. The authors present the history of a 70-year-old female, who underwent complex oncosurgical treatment of a locally advanced rectum carcinoma and a pure laparoscopic resection of a solitary hepatic metastasis of segment VII. With this case report the authors want to underline that malignant lesions in the posterior segments of the liver can be removed safely with laparoscopy.
Introduction: Thrombocytosis accompanying solid tumors and predicting the prognosis of malignant tumors has been the subject of intensive research lately. Reports so far have evaluated the role of preoperative platelet count. In our present study we looked at the effect of tumor removal on platelet count and the predictive power of postoperative thrombocytosis on the survival of patients with colorectal cancer (CRC).Methods: We retrospectively evaluated the clinical and histopathological data of 336 patients operated due to CRC between 2001 and 2011. Thrombocytosis was defined as a platelet count exceeding 400 x 10(3)/mL. Preoperative platelet count was compared with the value measured 1 month postoperatively.Results: The platelet count significantly decreased after the removal of the primary tumor (paired Wilcoxon test p < 0.001). In univariate analysis preoperative thrombocytosis was a significant marker of overall survival (OS) with HR 2.2, p < 0.001 while the postoperative thrombocytosis was nearly significant with HR = 1.59, p = 0.087. In multivariate setting, when corrected for location, stage, tumor size and controlling for gender and age (>65 years vs. <= 65 years), both pre- and postoperative thrombocytosis were significant independent prognostic markers with HR 1.80, p = 0.20 and HR = 1.98, p = 0.018, respectively.Discussion and conclusion: Although the pathomechanism of thrombocytosis related to solid tumors is not known the decrease of platelet count after the removal of the primary tumor raises the possibility that the tumor may play an active role in the development of thrombocytosis. Furthermore, the observation of postoperative thrombocytosis with significant worse outcome underlines the predictive power of elevated platelet count. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.
There is increasing evidence that thrombocytosis is associated with tumor invasion and metastasis formation. It was shown in several solid tumor types that thrombocytosis prognosticates cancer progression. The aim of this study was to evaluate preoperative thrombocytosis as a potential prognostic biomarker in isolated metastases, in patients with liver metastasis of colorectal cancer (mCRC). Clinicopathological data of 166 patients with mCRC who had surgical resection between 2001 and 2011 were collected retrospectively. All primary tumors have been already resected. The platelet count was evaluated based on the standard preoperative blood profile. The patients were followed-up on average for 28 months. Overall survival (OS) of patients with thrombocytosis was significantly worse both in univariate (HR = 3.00, p = 0.03) and in multivariate analysis (HR = 4.68, p = 0.056) when adjusted for gender, age, tumor size and surgical margin. Thrombocytosis was also a good prognosticator of disease-free survival (DFS) with HR = 2.7, p = 0.018 and nearly significant in multivariate setting (HR = 2.26, p = 0.073). The platelet count is a valuable prognostic marker for the survival in patients with mCRC.
Summary The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathological data of 10 years were collected retrospectively from 336 patients with CRC and 118 patients with mCRC. Both in the CRC and the mCRC group overall survival (OS) was significantly worse in patients who had elevated platelet count (hazard ratio [HR] = 2.2, p < 0.001 and HR = 2.9, p = 0.018, respectively). Multivariate analysis indicated that elevated platelet count was an independent prognostic factor of CRC (HR = 1.7, p = 0.035) and mCRC (HR = 3.1, p = 0.017). Disease-free survival (DFS) was significantly worse in patients with elevated platelet count in the CRC group (HR = 2.0, p = 0.011). In the multivariate analysis the PLR was not a prognostic factor in either of the two cohorts (HR = 0.92, p < 0.001 and HR = 0.89, p = 0.789, respectively). The platelet count is a valuable prognostic marker for the survival in patients both with CRC and mCRC while the PLR is not prognostic in either group.
A Wernicke-encephalopathia (vagy mas leirasokban: Wernicke–Korsakoff-encephalopathia) a belgyogyaszati gyakorlatban ritkan felismert korkep, amit B1-vitamin-hiany okoz. Tipusos formajat jellegzetes triasz kiseri (zavartsag, szemmozgaszavar, ataxia), gyakoribb azonban, hogy e tunetekbol csak a zavartsag van jelen. Leggyakrabban kronikus alkoholfogyasztokon figyelheto meg, de tarsulhat – mas korkepek mellett - vegstadiumu tumoros betegsegekhez is, ahol a zavart viselkedesnek szamtalan egyeb oka is lehet. A szerzok idos, elorehaladott gyomortumorban szenvedo ferfi betegen eszlelt Wernicke-encephalopathias esetuket ismertetik, felhivva a figyelmet a korismezes es a differencialdiagnosztika nehezsegeire. Orv. Hetil., 2014, 155(1), 30–33. | Wernicke encephalopathy (or Wernicke–Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke’s disease. Orv. Hetil., 2014, 155(1), 30–33.
INTRODUCTIONGleason grading is the most common method of prostate cancer classification.AIMThe aim of the authors was to assess the reproducibility of Gleason grading among pathologists using the same needle biopsy samples.METHOD23 pathologists examined 37 prostate cancer biopsies stained with hematoxylin and eosin. Gleason scores were categorised into 4 groups (2-4, 5-6, 7 and 8-10). Kappa statistics were used to reflect interobserver agreement.RESULTSConsidering all participating pathologists, grouping into one of the 4 categories resulted in an overall kappa value of 0.49. For the individual categories, the worst agreement (kappa = 0.15) was seen with well differentiated carcinomas, and the best (kappa = 0.65) with poorly differentiated ones.CONCLUSIONSThese results suggest that Gleason grading in biopsy samples is moderately reproducible. The kappa values vary according to the differentiation of the cancer, and there is not much difference between the results of the present study and those published in the literature. To increase reproducibility, trainings should be organised, and this could improve the quality of grading.
Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease.
Insul(in)oma is a usually solitary or, in some cases, multifocal tumor of pancreatic beta cells. It may be a component of multiple endocrine neoplasia type 1. or von Hippel-Lindau syndrome. In typical forms the diagnosis - based on the Whipple triad - is simple, however, it may be difficult to recognize in cases with near normal or only slightly elevated serum insulin levels, as well as in patients with known convulsive episodes. With the case presentation of an 81-year-old woman the authors draw attention to the pitfalls of the correct diagnosis. A special feature of the presented case is that convulsions persisted after surgical removal of the pancreatic neuroendocrine tumor verified with functional and imaging methods. Recurrent or residual tumor was not found, and morphological damage of the brain was absent. In the background of the continuing convulsions cerebrovascular alterations as well as the cytotoxic effect of the hypoglycemia-induced excessive glutamate production can be postulated.
The primary and metastatic gastrointestinal synovial sarcoma is rare with a wide differential diagnosis. It usually expresses cytokeratins EMA, BCL2 with an occasional CD99, and S100 positivity but not desmin. We present a case of metastatic synovial sarcoma with unusual immunophenotype causing diagnostic challenges. The tumor cells showed focal cytokeratin, EMA, and, unexpectedly, desmin positivity. Additional intranuclear TLE-1 positivity and negativity for CD34 and DOG-1 were also identified. A diagnosis of monophasic synovial sarcoma was confirmed by using FISH break-apart probe. RT-PCR revealed the SYT-SSX1 fusion gene. Intra-abdominal synovial sarcoma, either primary or metastatic, with unusual desmin positivity raises the diagnostic challenge, since a wide range of differential diagnoses could show a similar immunophenotype (leiomyosarcoma, desmoid tumor, myofibroblastic tumor, and rarely GIST etc.). Typical morphology and focal cytokeratin/EMA positivity should alert to this tumor, and FISH and RT-PCR remain the gold standard for the confirmation.
In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical phenotype as a surrogate for the genetic subtype, 11 luminal A, 3 luminal B, 3 triple negative and one HER2+ cases were included. Ten genes were significantly downregulated in tumors compared with normal breast tissues (CLDNs 5, 10, 16, 18, 19, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3), whereas one gene (CLDN17) was significantly up-regulated in tumors when compared with normal breast. At protein level CLDNs 5, 10, 16, 18, ZO-1 and ZO-2 were downregulated in tumors as compared with normal breast tissue. CLDN17 showed variable expression in tumor tissues in comparison to normal breast. In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated. We found altered TJ genes and proteins whose expression has not yet been associated with breast carcinoma. Our findings show a tendency of TJ genes and proteins to be downregulated in breast cancer. Further studies are necessary to examine whether the downregulation of the above mentioned TJ associated genes and proteins may contribute to the malignant progression of invasive ductal breast carcinomas.