Transitional Cell Differentiation Research Articles

Primary transitional cell carcinoma of the endometrium: Case report of a rare tumor

ABSTRACT Primary transitional cell carcinoma of endometrium or an endometrial carcinoma with an extensive transitional cell differentiation is an extremely rare entity and always poses a diagnostic and therapeutic challenge to clinicians and pathologists. We present a 70-year-old lady who presented with postmenopausal bleeding. Grossly, a gray white tumor was identified in the fundus region of the uterus and was invading >50% into the myometrium. Histopathological sections examined from the tumor showed a highly cellular tumor arranged in nests and tightly packed papillary structures with thin fibrovascular cores covered by multilayered polygonal cells. On immunohistochemistry, the tumor cells were positive for CK7, ER, vimentin, and focally positive for p16. The present case was reported to emphasize its clinical and histological features which will broaden the morphological spectrum of epithelial neoplasms of endometrium.

P53 governs an AT1 differentiation programme in lung cancer suppression.

Lung cancer is the leading cause of cancer deaths worldwide1. Mutations in the tumour suppressor gene TP53 occur in 50% of lung adenocarcinomas (LUADs) and are linked to poor prognosis1-4, but how p53 suppresses LUAD development remains enigmatic. We show here that p53 suppresses LUAD by governing cell state, specifically by promoting alveolar type 1 (AT1) differentiation. Using mice that express oncogenic Kras and null, wild-type or hypermorphic Trp53 alleles in alveolar type 2 (AT2) cells, we observed graded effects of p53 on LUAD initiation and progression. RNA sequencing and ATAC sequencing of LUAD cells uncovered a p53-induced AT1 differentiation programme during tumour suppression in vivo through direct DNA binding, chromatin remodelling and inductionof genes characteristic of AT1 cells. Single-cell transcriptomics analyses revealed that during LUAD evolution, p53 promotes AT1 differentiation throughaction in a transitional cell state analogous to a transient intermediary seen during AT2-to-AT1 cell differentiation in alveolar injury repair. Notably, p53 inactivation results in the inappropriate persistence of these transitional cancer cells accompanied by upregulated growth signalling and divergence from lung lineage identity, characteristics associated with LUAD progression. Analysis of Trp53 wild-type and Trp53-null mice showed that p53 also directs alveolar regeneration after injury by regulating AT2 cell self-renewal and promoting transitional cell differentiation into AT1 cells. Collectively, these findings illuminate mechanisms of p53-mediated LUAD suppression, in which p53 governs alveolar differentiation, and suggest that tumour suppression reflects a fundamental role of p53 in orchestrating tissue repair after injury.

Epithelial expression of Gata4 and Sox2 regulates specification of the squamous\u2013columnar junction via MAPK/ERK signaling in mice

The squamous–columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal–distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells within the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.

Advanced Stage of Primary Transitional-Cell Carcinoma of the Endometrium: A Case Report and Literature Review

Abstract Background: Primary transitional cell carcinoma (TCC) of the endometrium and endometrial carcinoma with transitional-cell differentiation are rare entities with only 21 cases reported in t...

Benign and Malignant Brenner Tumors Show an Absence of TERT Promoter Mutations That Are Commonly Present in Urothelial Carcinoma.

Brenner tumors are uncommon ovarian neoplasms, which have morphologic and immunophenotypical features of transitional cell (urothelial) differentiation. The origin of Brenner tumors is perplexing, but they are believed to arise from transitional cell metaplasia occurring within the ovary and/or fallopian tube, although it is controversial whether this metaplasia is truly along transitional cell lines. Recently, TERT promoter mutations have been identified in urothelial carcinoma (UC) with high frequency (approximately 70%), and the current literature suggests a potential diagnostic and/or prognostic role of these mutations in UC. Molecular evidence supporting that Brenner tumors represent neoplasms exhibiting transitional cell differentiation is scant. To explore this further, we investigated a series of 19 Brenner tumors of the ovary (15 benign and 4 malignant) for the presence of TERT promoter mutations after genomic DNA extraction from formalin-fixed paraffin-embedded tissue blocks and standard polymerase chain reaction sequencing. TERT promoter mutations were not identified in any of the cases (0/19). The absence of TERT promoter mutations in Brenner tumors suggests that despite the morphologic and some immunophenotypical resemblance to non-neoplastic and neoplastic transitional epithelium, Brenner tumors may exhibit a molecularly distinct pathogenesis. The findings also may portend diagnostic utility in rare cases wherein it is difficult to distinguish a primary malignant Brenner tumor of the ovary from metastatic UC.

Squamous Cell Malignancies of the Upper Urinary Tract: A Survival Study and a Systematic Review of the Literature

Background: Carcinomas of the renal pelvis and ureter are rare diseases. Previous reports suggest that squamous cell histology is associated with inferior survival. We present one of the largest population based analysis to date of survival in patients with upper urinary tract malignancies and a systematic review of the subject. Methods: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2004 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 3.7 (95% CI 3.0-4.5) for SCC when compared to TCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (p = 0.84) and for patients with clear lymph nodes (p = 0.92). Conclusions: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.

Primary Endometrioid Carcinoma of the Broad Ligament: A Rare Case Report

Although secondary involvement of the broad ligament by malignant tumours arising elsewhere in the abdomen is common, primary tumours in this location are rare. Most neoplasms in this region whether benign or malignant usually present clinically with vague symptoms and are often discovered either during a routine gynaecological examination or on abdominal exploration because of the presence of a pelvic mass and vague lower abdominal discomfort or pain [1]. The present case which was diagnosed clinically as left ovarian tumour and histopathologically as endometrioid carcinoma of the broad ligament is reported for its rarity and for the unique histological finding of transitional cell differentiation associated with the primary tumour.

Survival of Patients with Squamous Cell Malignancies of the Upper Urinary Tract

BackgroundCarcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies.MethodsWe analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis.ResultsWe identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 3.7 (95% CI 3.0–4.5) for SCC when compared to TCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (P = 0.84) and for patients with clear lymph nodes (P = 0.92).ConclusionsSCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage.

Metaplastic carcinoma of the breast-A rare neoplasm with transitional cell differentiation: An exceptional feature

Metaplastic carcinomas of the breast are malignant breast neoplasms composed of a mixture of both epithelial and mesenchymal elements. The rarity of this tumor is exemplified by the fact that it accounts for only about 0.2% of all breast carcinomas. It can present histologically with diverse differentiation and the exact histogenesis of these tumors is unknown. The present case is reported for its rarity and for the presence of transitional cell differentiation along with the other usual components of metaplastic carcinoma. Transitional cell differentiation in a metaplastic carcinoma has not been documented in the literature. Besides this, it highlights the importance of special stains and immunohistochemistry in evaluating these carcinomas and the need for early diagnosis and excision of these tumors as these carcinomas generally have a poorer prognosis as compared to breast carcinomas without metaplasia, with the tumor size having an important bearing on the outcome of this condition.

Is squamous cell histology an adverse prognosticator for survival of malignancies of the upper urinary tract?

6617 Background: Carcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies. Methods: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 0.42 (95% CI 0.36–0.47) for TCC when compared to SCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (p = 0.84) and for patients with clear lymph nodes (p = 0.92). Conclusions: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage. No significant financial relationships to disclose.

Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation: a clinicopathologic study of 5 cases and review of the literature

To date, only 16 cases of transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation have been reported in the literature. We reviewed the clinicopathologic features of 5 cases of endometrial carcinoma with transitional cell differentiation. The mean age was 68 years, and all patients presented with postmenopausal bleeding. Macroscopically, the tumors were intracavitary and friable. Microscopically, the tumors were composed of tightly packed papillary structures with thin fibrovascular cores, resembling a transitional cell carcinoma of the urinary tract. One tumor showed exclusively transitional cell differentiation, whereas the remaining 4 neoplasms showed that the transitional cell carcinoma was admixed with a variable proportions of endometrioid adenocarcinoma. Four cases were in FIGO stage IB, whereas the remaining tumor infiltrated the uterine cervix (FIGO stage IIB). Immunoreactivity was typical of müllerian derivatives (cytokeratin 7 positive, cytokeratin 20 negative). p16 protein was positive in all cases, but human papillomavirus DNA was not detected in any of the tumors. None of the patients developed local recurrence or distant metastases, even though there are too few cases of transitional cell carcinoma of the endometrium reported to make any statistically valid conclusions about response to therapy and prognosis. Transitional cell carcinoma is an unusual variant of endometrial carcinoma, with distinctive histologic and immunophenotypic features. Identification of this variant broadens the morphological spectrum of epithelial neoplasms of the endometrium.

MP-13.09: Proliferation and differentiation of renal urothelial transitional cells (RUTEC) after unilateral ureteral obstruction

MP-13.09: Proliferation and differentiation of renal urothelial transitional cells (RUTEC) after unilateral ureteral obstruction

Immunohistochemical features of a papillary squamous cell carcinoma of the endometrium with transitional cell differentiation

An 84-year-old woman underwent hysterectomy due to a friable endometrial mass infiltrating almost half way through the myometrial wall. The tumor consisted of papillary structures with thin fibrovascular cores covered by several layers of pleomorphic cells. The deeply located neoplastic cells were ovoid with a pale eosinophilic cytoplasm resembling urothelial cells. A diagnosis of papillary squamous cell carcinoma of the endometrium with transitional cell differentiation was made. Although she recovered well after surgery, she died one year later because of disseminated disease. In an attempt to obtain new insights into the physiopathology of this very rare tumor, an immunohistochemical panel with 32 markers was performed. The neoplastic cells were positive for cytokeratin 5, vimentin, p63, p21, VEGF, Ki67, BAG1, and bcl-2. The expression of BAG-1 and bcl-2 may suggest that anti-apoptotic stimuli are preponderant in this neoplasm.

Characterization of Papillary Squamotransitional Cell Carcinoma of the Cervix

Does papillary squamotransitional cell carcinoma (PSTCC) behave differently from conventional squamous cell carcinoma of the cervix and does PSTCC have true transitional cell differentiation? Twenty cases of PSTCC were identified from archival files. Clinical data were compiled. Immunoperoxidase stains for uroplakin III, p63 and p16 were performed on available tissue blocks. Patients ranged in age from 27 to 85 years. Twelve patients were FIGO Stage I, 4 were Stage II, and 2 were Stage III. Thirteen patients had clinical follow-up ranging from 5 to 132 months. Three patients subsequently had more extensive disease than initial clinical staging indicated. Nine patients had no tumor progression, three had local recurrence and one had metastatic disease. Eight cases were strongly immunoreactive for p63 and p16 and 14 were negative for uroplakin III. PSTCC lacks true transitional cell differentiation and probably shares similar clinicopathologic features with conventional cervical squamous cell carcinoma.

Immunoprofile of ovarian tumors with putative transitional cell (urothelial) differentiation using novel urothelial markers: histogenetic and diagnostic implications.

Ovarian tumors containing cells with transitional cell morphology are recognized in the 1999 World Health Organization classification of ovarian tumors and include benign Brenner tumor, borderline and malignant Brenner tumor, and transitional cell carcinoma. Recent immunohistochemical investigations have reached conflicting conclusions regarding true urothelial differentiation in ovarian Brenner tumors. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and Wilms' tumor protein (WT1) to study urothelial differentiation in ovarian transitional cell tumors. Additionally, we compared the immunohistochemical profile of transitional cell carcinoma of the ovary (TCC-O) with that of transitional cell carcinoma of the bladder (TCC-B), to ascertain if immunohistochemistry may aid in distinguishing primary from metastatic TCC-O. Seventeen benign Brenner tumors and 17 TCC-O were stained with antibodies to UROIII, THR, CK7, CK20, and WT1. Additionally, 6 Brenner tumors of borderline malignancy were stained with antibodies to UROIII, THR, CK7, and CK20. The immunohistochemical results were compared with those of 30 cases of noninvasive TCC-B (low malignant potential n=14, low grade n=16) and 36 cases of invasive TCC-B stained with a similar panel of antibodies as part of another study. Twenty-one nontransitional cell ovarian carcinomas (9 serous, 4 clear cell, 5 endometrioid, 2 mixed endometrioid/serous, and 1 mucinous) were used as controls. Most Brenner tumors showed positivity with UROIII (82%) and THR (76%), supporting true urothelial differentiation in these tumors. Although TCC-O has considerable morphologic overlap with TCC-B, they had only partial immunophenotypic overlap. TCC-O rarely expressed UROIII (6%) and THR (18%) and none expressed CK20. In contrast, nearly 40% of invasive TCC-B expressed UROIII, 61% expressed THR, and 50% expressed CK20. Nearly 82% of TCC-O expressed WT1, which was negative in all TCC-B. Our results may have diagnostic value in distinguishing TCC-O (CK20-, UROIII-/+, WT1+) and invasive TCC-B (CK20+, UROIII+/-, WT1-) metastatic to the ovary. They also indicate that the morphologic similarity between TCC-O and TCC-B does not indicate any histogenic similarity and, as others have noted, TCC-O is a variant morphology in the spectrum of surface epithelial carcinomas.

Immunohistochemical Analysis of Uroplakins, Urothelial Specific Proteins, in Ovarian Brenner Tumors, Normal Tissues, and Benign and Neoplastic Lesions of the Female Genital Tract

Uroplakins are the characteristic integral membrane proteins in terminally differentiated, superficial urothelial asymmetric unit membrane. Brenner tumors of the ovary and Walthard cell nests of Fallopian tubes have been considered to represent urothelial differentiation in the female genital tract, but no definitive differentiation marker has been demonstrated supporting such a conclusion. An immunohistochemical analysis was performed to assess the expression of uroplakins in these lesions as well as in various benign and neoplastic lesions and normal tissues of the female genital tract. Focal expression of uroplakins was observed on the luminal surface of ovarian Brenner tumor cells forming microcysts in all 5 cases examined. In contrast, uroplakins were slightly expressed in only 1 of 12 cases of Walthard cell nests, even in the presence of microcyst formation. Uroplakins were not expressed in other benign or malignant lesions or normal tissues of the female genital tract. These results support the hypothesis that the Brenner tumor and possibly Walthard cell nests represent urothelial (transitional cell) differentiation.

Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation

BACKGROUND Transitional cell carcinoma (TCC) is rare in the female genital tract. Although it is most common in the ovary, small series of cases in the cervix have been reported, with isolated cases described in the fallopian tube, adnexa uteri, and endometrium. METHODS Eight cases of primary TCC involving the endometrium and 1 case of ovarian TCC metastatic to the endometrium were retrieved from the files of the Armed Forces Institute of Pathology and the University of Texas Southwestern Medical Center. Cases were selected based on the presence of endometrial TCC, whether pure or combined with other patterns, and regardless of the relative amount. Immunostaining for cytokeratins 7 and 20 was performed. RESULTS Among the 8 women with primary endometrial tumors, the mean age was 61.6 years (range, 41-83 years). Uterine bleeding was the presenting symptom in 7 women. Macroscopically, the tumors were polypoid, and infiltrated the myometrium, although the extent of infiltration varied. Seven endometrial tumors showed a papillary component. TCC was always admixed with other patterns (predominantly squamous, but also endometrioid, papillary, and serous patterns), with the proportion of the TCC component ranging from 5% to 95% (mean, 63.8%). TCC was the main invasive pattern observed in all three of the cases that had deep myometrial invasion; these cases also had vascular invasion. Seven tumors were confined to the uterus; one was metastatic to the ovary. The ovarian TCC metastatic to the endometrium had a pure TCC pattern. Five of 7 cases of TCC had cytokeratin 7+/20- immunoreactivity; 2 cases were cytokeratin 7-/20-. Treatment of primary endometrial tumors was mainly surgical, with adjuvant radiation therapy in 4 cases or chemotherapy in 1 case. Survival ranged from 3 months to 12.9 years (mean, 5.1 years). Of five women for whom follow-up was available, three were alive with no evidence of disease, one was alive with a local recurrence, and one died of unrelated disease. CONCLUSIONS TCC is a rare, distinct subtype of endometrial carcinoma with morphologic features of urothelial differentiation, but retention of a mullerian immunoprofile. While the overall prognosis does not appear to be worse than what might be anticipated for the stage of tumor present, TCC appears to be the more aggressive histologic subtype among the patterns with which it is admixed. Cancer 1997; 79:1933-43. © 1997 American Cancer Society.

Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation

Transitional cell carcinoma (TCC) is rare in the female genital tract. Although it is most common in the ovary, small series of cases in the cervix have been reported, with isolated cases described in the fallopian tube, adnexa uteri, and endometrium. Eight cases of primary TCC involving the endometrium and 1 case of ovarian TCC metastatic to the endometrium were retrieved from the files of the Armed Forces Institute of Pathology and the University of Texas Southwestern Medical Center. Cases were selected based on the presence of endometrial TCC, whether pure or combined with other patterns, and regardless of the relative amount. Immunostaining for cytokeratins 7 and 20 was performed. Among the 8 women with primary endometrial tumors, the mean age was 61.6 years (range, 41-83 years). Uterine bleeding was the presenting symptom in 7 women. Macroscopically, the tumors were polypoid, and infiltrated the myometrium, although the extent of infiltration varied. Seven endometrial tumors showed a papillary component. TCC was always admixed with other patterns (predominantly squamous, but also endometrioid, papillary, and serous patterns), with the proportion of the TCC component ranging from 5% to 95% (mean, 63.8%). TCC was the main invasive pattern observed in all three of the cases that had deep myometrial invasion; these cases also had vascular invasion. Seven tumors were confined to the uterus; one was metastatic to the ovary. The ovarian TCC metastatic to the endometrium had a pure TCC pattern. Five of 7 cases of TCC had cytokeratin 7+/20- immunoreactivity; 2 cases were cytokeratin 7-/20-. Treatment of primary endometrial tumors was mainly surgical, with adjuvant radiation therapy in 4 cases or chemotherapy in 1 case. Survival ranged from 3 months to 12.9 years (mean, 5.1 years). Of five women for whom follow-up was available, three were alive with no evidence of disease, one was alive with a local recurrence, and one died of unrelated disease. TCC is a rare, distinct subtype of endometrial carcinoma with morphologic features of urothelial differentiation, but retention of a mullerian immunoprofile. While the overall prognosis does not appear to be worse than what might be anticipated for the stage of tumor present, TCC appears to be the more aggressive histologic subtype among the patterns with which it is admixed.

Characterization of prostatic basal cell hyperplasia and neoplasia in aged macaques: Comparative pathology in human and nonhuman primates

There are very few reports of proliferative prostatic lesions occurring spontaneously in nonhuman primates. We found that 15 of 19 glands in aged macaques contained one or more epithelial lesions in the cranial lobe. These originated in the basal cell compartment and were characterized as hyperplasia and benign neoplasia. The adenomas contained variable gland formation, with morphologic and immunohistochemical evidence of secretory, mucigenous, neuroendocrine, transitional, and squamous cell differentiation. These cell types are resident in the normal prostate or appear in metaplastic lesions, and their presence in the macaque tumors is consistent with differentiation of a stem cell along multiple phenotypic pathways. The macaque growths are similar to human prostatic basal cell lesions and could provide insights into their pathogenesis as well as cellular ontogeny and general mechanisms of carcinogenesis in this organ.

Reconstruction of the Urinary Bladder Mucosa in Three-Dimensional Collagen Gel Culture: Fibroblast-Extracellular Matrix Interactions on the Differentiation of Transitional Epithelial Cells

The purpose of this study was to reconstruct a urinary bladder mucosa in three-dimensional collagen gel culture conditions that included fibroblasts. Transitional epithelial cells and fibroblasts, isolated respectively from the epithelial and lamina propria layers of porcine urinary bladder, were cultured in monolayer. These fibroblasts were embedded and cultured within a collagen gel matrix to reconstruct a lamina propria. The isolated transitional epithelial cells were then seeded in vitro on this reconstructed lamina propria on which the transitional epithelial cells formed a stratified urothelium composed of basal, intermediate and superficial layers. Urothelial differentiation was observed only on the fibroblast-containing collagen matrix. Differentiation did not occur on a cell-free collagen matrix through use of fibroblast conditioned medium. Thus, urothelial differentiation depended upon a fibroblast-extracellular matrix interaction. The differentiated transitional epithelial cell layer thus produced closely resembled a urothelium in vivo. This culture model may provide a useful system in which to study various diseases of the urinary bladder.