scholarly journals Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Tim Mandelkow ◽  
Niclas C. Blessin ◽  
Eva Lueerss ◽  
Laura Pott ◽  
Ronald Simon ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Cell Density ◽  
Small Cell Carcinoma ◽  
Immune Cell ◽  
Cell Cancer ◽  
Small Cell ◽  
Urothelial Carcinomas ◽  
Significant Difference ◽  
Cell Bladder Cancer

Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response including PD-L1 expression and the quantity and location of tumor-infiltrating lymphocytes (TILs) in 12 small-cell and 69 “classical” urothelial cancers by immunohistochemistry. The analysis revealed that small-cell carcinomas were characterized by the virtual absence of PD-L1 expression and an “immune-excluded” phenotype with only a few TILs in the center of the tumor (CT). In small-cell carcinomas, the average immune cell density in the CT (CD3: 159±206, CD8: 87±169 cells/mm2) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625±800, p<0.001; CD8: 362±626 cells/mm2, p=0.004) while there was no significant difference in the immune cell density at the invasive margin (IM) (small-cell carcinomas CD3: 899±733, CD8: 404±433 cells/mm2; urothelial carcinomas CD3: 1167±1206, p=0.31; CD8: 582±864 cells/mm2, p=0.27). Positive PD-L1 staining was found in 39% of urothelial cancers, but in only 8% of small-cell bladder cancer cases (p=0.04). Concordant with these data, a sharp decrease of PD-L1 positivity from >80% to 0% positive cells and of TILS in the CT from 466-1063 CD3-positive cells/mm2 to 50-109 CD3-positive cells/mm2 was observed in two cancers with clear-cut progression from “classical” urothelial to small-cell carcinoma. In conclusion, these data demonstrate that small-cell bladder cancer commonly exhibits an immune-excluded phenotype.

Expression of cadherins, p53, and BCL2 in small cell carcinomas of the cervix: Potential tumor suppressor role for N-cadherin

2003 ◽  
Vol 13 (2) ◽  
pp. 240-243 ◽  
Author(s):  
T. A. Zarka ◽  
A. C. Han ◽  
M. I. Edelson ◽  
N. G. Rosenblum
Keyword(s):  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Cell Cancer ◽  
Small Cell ◽  
Specific Cell ◽  
Nuclear Staining ◽  
Cytoplasmic Staining ◽  
Significant Difference ◽  
E Cadherin

Cadherins are tissue-specific cell adhesion molecules that function as tumor suppressors. Analysis of cadherin expression is useful for differentiation of tumor histogenesis, and because they serve as markers of tumor behavior and prognosis. Since the pattern of cadherin expression is not well characterized for small cell carcinoma of the cervix, we examined cases of these tumors for expression of cadherins, and two other oncoproteins p53 and BCL2. Four cases of small cell neuroendocrine carcinomas were identified from the Gynecologic Oncology Service with diagnoses confirmed by immunohistochemistry for neuroendocrine markers. Archival paraffin blocks were studied by heat-enhanced immunohistochemistry using commercially available antibodies specific for E-cadherin, P-cadherin, and N-cadherin, p53, and BCL2. Sections were examined for specific membrane staining of cadherins, nuclear staining of p53, and cytoplasmic staining of BCL2. E-cadherin was expressed in three of four cases, P-cadherin in one of four, and N-cadherin in none of four cases. P53 was expressed in one of four cases and BCL2 in one of four cases. The four cases showed three different patterns of immunohistochemical staining for the five oncoproteins. Specifically, two cases expressed E-cadherin only; one case lacked all three cadherins, was negative for BCL2, and was only positive for p53; and one case expressed E- and P-cadherin and BCL2. Prior studies of other neuroendocrine and small cell tumors of other organs showed E-cadherin expressed in 98% (42 /43), N-cadherin in 65% (28/43), and P-cadherin in 40% (17/43) of cases. Additionally, one case of vaginal small cell carcinoma showed expression of all three cadherins. The only significant difference between cervical primaries and other primary sites is that N-cadherin was not detected in our four cases vs. 65% expression in other sites (P < 0.001). We conclude that cadherin and oncoprotein profiles in small cell carcinoma of the cervix are different in the four cases analyzed. Additional cases need to be studied to determine the specificity and frequency of these oncoprotein profiles for small cell carcinoma of the cervix. These may possibly represent different oncogenic pathways in development of small cell cancer of the cervix. Also, our results suggest that N-cadherin may be a tumor suppressor gene in these tumors.

scholarly journals A Case of Primary Small-Cell Carcinoma of the Bladder

2016 ◽  
Vol 9 (3) ◽  
pp. 574-579 ◽  
Author(s):  
Ashita Ono ◽  
Yosuke Hirasawa ◽  
Mitsumasa Yamashina ◽  
Naoto Kaburagi ◽  
Takashi Mima ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Cell Carcinoma ◽  
Radical Cystectomy ◽  
Small Cell Carcinoma ◽  
Distant Metastasis ◽  
Small Cell ◽  
Common Type ◽  
Cell Of Origin ◽  
Carcinoma Of The Bladder

Primary small-cell carcinoma arising from the bladder (SmCCB) is uncommon. It differs from urothelial carcinoma (UC), the most common type of bladder cancer, with respect to its cell of origin, biology, and prognosis. Biologically, prostatic SmCCB is much more aggressive than UC, and the prognosis for cases with distant metastasis is especially poor. We report here a case of primary SmCCB (cT3bN1M0) treated with radical cystectomy.

Impact of histologic subtype on bladder cancer outcome.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 391-391
Author(s):  
Samuel L Washington ◽  
Thomas Sanford ◽  
Michael S. Leapman ◽  
Maxwell V. Meng ◽  
Sima P. Porten
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Radical Cystectomy ◽  
Small Cell Carcinoma ◽  
Squamous Cell ◽  
Small Cell ◽  
Variant Histology ◽  
The Impact

391 Background: Variant histology is increasingly recognized but its impact on outcomes is less well known compared to urothelial carcinoma (UC). We aim to evaluate the impact of variant histology on bladder cancer outcomes using the National Cancer Database (NCDB), a U.S. population-based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods: We identified patients with bladder cancer from 2004 to 2013 treated with radical cystectomy. We compared clinical and pathologic characteristics between those with UC and those with variant histology. Chi-square test was utilized for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used with hazard ratios (HR) and 95% confidence intervals (CI) to identify independent predictors of overall survival. Results: A total of 40,918 patients were identified with mean age 67 years, with male (75%) and Caucasian (90.9%) predominance. Median follow-up was 36.9 months (IQR 16.1-67.5). Squamous cell carcinoma (4.4%), small cell carcinoma (1.6%) and micropapillary (0.9%) were the most common variant histologies. Variant histology was found more commonly in women (35.6% vs 23.4%, p < 0.05), black (8.8% vs 5.6%, p < 0.05), stage pT3 or T4 (67% vs 50.2%, p < 0.05) and node positive (30.8% vs 26.9%, p < 0.05). In adjusted models squamous cell carcinoma (HR 1.3, 95% CI 1.2-1.4), small cell carcinoma (HR 1.6, 95% CI 1.5-1.8) and black ethnicity (HR 1.2, 95% CI 1.1-1.2) were independent predictors of increased mortality risk while micropapillary was associated with decreased risk (HR 0.8, 95% CI 0.7-1.0) after controlling for age, gender, surgical margin status, pathologic T stage, pathologic N stage and history of chemotherapy. All associations remained statistically significant (p < 0.05). Conclusions: Non-urothelial histology was associated with worse overall survival in patients with bladder cancer treated with radical cystectomy; however, contrary to some previous reports, micropapillary variant was associated with lower risk of death. In addition, black ethnicity was associated with worse survival. Further investigation is needed to explore the impact of variant histology as well as other socioeconomic factors on survival after cystectomy.

Young patients with bladder cancer: Outcomes from the National Cancer Database.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 380-380
Author(s):  
Samuel L Washington ◽  
Maxwell V. Meng ◽  
Sima P. Porten
Keyword(s):  
Squamous Cell Carcinoma ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Squamous Cell ◽  
Univariate Analysis ◽  
Young Patients ◽  
Small Cell ◽  
Categorical Variables ◽  
National Cancer Database

380 Background: Bladder cancer (BC) affecting young patients is not well characterized but seems to be increasingly diagnosed. We aim to describe pathologic findings and BC outcomes in patients less than 40 years old using the National Cancer Database (NCDB), a US population based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods: We identified 362,091 patients diagnosed with BC from 2004 to 2013. We compared demographic, clinical and pathologic information between those younger and older than 40 years. Univariate analysis was performed using Chi-square test for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used for survival analysis with hazard ratios (HR) and 95% confidence intervals (CI). Multivariable model was used to identify independent predictors of mortality (overall survival, OS). Results: 3,799 patients (1.1%) were 40 or younger with mean age of 34.5 years. Fewer young patients were women (25.2% vs 30.3%, p<0.001). More identified as nonwhite (11.6% vs 7.3%, p<0.001), had lower clinical T stage (cTa 51.4% vs 38.3%, cT1 13.3% vs 19.6; p<0.001), and longer median follow-up (46.4 months IQR 23.3-73.9 vs 35.3 months IQR 16.7-61.6). Age less than 40 (HR 0.3, 95% CI 0.2-0.3), chemotherapy (HR 0.9, 95% CI 0.9-0.9) and cystectomy (HR 0.8, 95% CI 0.8-0.9) were associated with decreased mortality when controlling for clinical characteristics (p<0.001). In sub-analysis of young patients with cystectomy, more had pT0 disease (20.3% vs 18.2%, p=0.005) with squamous cell carcinoma (13.6% vs 4%) and small cell (3.2% vs 1.6%) more prevalent (p<0.001). In adjusted models, squamous cell carcinoma (HR 1.1, 95% 1.1-1.2), small cell carcinoma (HR 1.5, 95% CI 1.4-1.7), RT (HR 1.2, 95% CI 1.!-1.3) and black ethnicity (HR 1.1, 95% CI 1.1-1.2) were independent predictors of worse OS. Conclusions: Younger patients with BC were more commonly non-white, men, and had low stage disease. In young patients undergoing cystectomy, squamous cell carcinoma, small cell carcinoma and black ethnicity were associated with worse OS. Further exploration in this younger patient cohort is needed to better characterize the optimal oncologic management for these patients.

Primary genitourinary small cell carcinoma: Clinicopathologic and survival outcomes from SEER database.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 200-200
Author(s):  
R. Thota ◽  
S. Birdsong ◽  
S. Subbiah
Keyword(s):  
Prostate Cancer ◽  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Renal Cancer ◽  
Small Cell ◽  
External Beam Radiation ◽  
Seer Database ◽  
Specific Mortality ◽  
Cancer Specific Mortality

200 Background: Small cell carcinoma of genitourinary system (SCC) is a highly aggressive and rare entity. The aim of the study is to characterize the clinicopathologic characteristics and evaluate the treatment outcomes of SCC in adult patients. Methods: Retrospective analysis of 732 patents diagnosed with small cell carcinoma of bladder from 1973 to 2007 was done via SEER database. Demographics, stage, type of treatment received and cancer-specific mortality were examined. Results: 732 patients were identified with SCC of genitourinary tract of which 341 were small cell bladder cancer, 336 were small cell prostate cancer and 55 were small cell renal cancer. Of these 644 patients were males and 88 were females. Median age of diagnosis is 73 years for bladder, 72 years for prostate and 70 years for renal cancer. Majority of the patients were Caucasians (89%) followed by African Americans (6%) and other races (4.98%). Grading of the tumor revealed that 12 patients had well differentiated tumor, 18 patients had moderately differentiated tumor, 191 patients had poorly differentiated, 292 patients had undifferentiated tumor and 219 patients had unknown grade. Pathological T-stages were as follows: T1= 34 (4.6%), T2= 102 (14%), T3= 43 (9%), T4= 41 (5.6%), 38.4% unknown T stage and 67 (9%) patients had metastatic disease. In majority of the patients the treatment received was unknown (565), 90 patients received external beam radiation, and 76 patients received surgery. Cancer-specific mortality was 54% in bladder cancer, 71% in prostate cancer and 78.6% in renal cancer. Median overall survival for all stages was 15.8 months in bladder cancer, 11.3 months in prostate cancer and 8 months in renal cancer. Conclusions: Results show that SCC is a highly aggressive tumor with poor prognosis. Clinical trials involving multiple institutes are needed to accrue enough patients so that treatment paradigms for this uncommon disease can be developed. No significant financial relationships to disclose.

Cisplatin plus Vindesine versus Cisplatin plus VP16 versus Doxorubicin plus Cytoxan in Non-Small-Cell Carcinoma of the Lung. A Randomized Study

1986 ◽  
Vol 72 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Adriano Paccagnella ◽  
Alba Brandes ◽  
Giovanni L. Pappagallo ◽  
Giuliana Simioni ◽  
Vinicio P. Fosser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Response Rate ◽  
Randomized Study ◽  
Therapeutic Strategies ◽  
Small Cell ◽  
Control Group ◽  
Significant Difference ◽  
Duration Of Response

From March 1981 to January 1984, 116 patienst with advanced non-small-cell carcinoma of the lung (NSCCL) were randomly assigned to 3 combinations as follows: CDDP + DVA, CDDP + VP16 and DXR + CTX. 94 patients were evaluable for response, 106 for toxicity and survival. Of 31 patients, 15 (48%; 3 CRs and 12 PRs) responded to CDDP + DVA; of 33 patients, 12 (36%, 2 CRs and 10 PRs) responded to CDDP + VP16; of 30 patients, 3 (10%) obtained a PR with DXR+CTX (CDDP+DVA vs DXR + CTX, P < 0.005; CDDP + VP16 vs DXR + CTX, P < 0.05; CDDP + DVA vs CDDP + VP16, P = NS). The median duration of response was 22 weeks in the CDDP-DVA group, 17 weeks in the CDDP-VP16 group, and 16 weeks in the DXR+CTX group. No significant difference in survival was observed among the 3 groups (median: 43, 47, 41 weeks, respectively). Hematologic and neurologic toxicities were significantly higher in the DVA-containing regimen. Despite the lack of improvement of overall survival with the CDDP-containing combinations over the DXR + CTX control group, the good response rate makes them suitable to be used in combined therapeutic strategies.

scholarly journals Case Report: Systemic Treatment and Serial Genomic Sequencing of Metastatic Prostate Adenocarcinoma Progressing to Small Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
XiaoJun Lu ◽  
Wenwen Gao ◽  
Yu Zhang ◽  
Tao Wang ◽  
Hongliang Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Carcinoma ◽  
Seminal Vesicle ◽  
Small Cell Carcinoma ◽  
Cell Cancer ◽  
Phylogenetic Reconstruction ◽  
Neuroendocrine Differentiation ◽  
Small Cell ◽  
Castration Resistance ◽  
Tumor Biopsy

Small cell carcinoma (SCC)/neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive subtype of prostate cancer associated with an AR(androgen receptor)-null phenotype and visceral metastases. This study presents a 44-year-old man originally diagnosed with metastatic hormone-sensitive prostatic adenocarcinoma. After 6-month androgen deprivation therapy (ADT) combined with docetaxel, the patient developed paraplegia. Laminectomy was performed, and a thoracic vertebral biopsy revealed neuroendocrine differentiation and mixed adenocarcinoma. The patient developed liver metastases and experienced stable disease for 4 months following etoposide combined with cisplatin and pembrolizumab. Seminal vesicle biopsy after chemotherapy revealed small-cell cancer. The prostate biopsy specimen also indicated pure SCC. We witnessed the dynamic evolution from pure adenocarcinoma to fully differentiated SCC, leading to obstruction and death. In addition, whole-exome sequencing was performed on both biopsy specimens of the thoracic vertebra at the beginning of castration resistance and that of seminal vesicle after multiple lines of treatment failure. Utilizing phylogenetic reconstruction, we observed that both samples shared a common ancestor clone harboring aberrations in the TP53, RB1, and NF2 genes. We also discovered that driver events in the private subclones of both samples, such as alterations in CDC27 and RUNX1, might have played a significant role in tumor progression or even neuroendocrine differentiation. Tumor biopsy and IHC assessment must be repeated at different stages of progression, because of intrapatient spatial and temporal heterogeneity of adenocarcinoma versus SCC/NEPC. Although, typical treatments including ADT, docetaxel, etoposide, cisplatin, and pembrolizumab provided temporary response, the patient still had a poor prognosis.

Epidemiology and survival of small cell carcinoma of gastrointestional tract: A Surveillance, Epidemiology, and End Results (SEER) database review.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 518-518
Author(s):  
Abhijeet Kumar ◽  
Srinath Sundararajan ◽  
Haiyan Cui ◽  
Hitendra Patel ◽  
Emad Elquza
Keyword(s):  
Survival Rate ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Paired Comparison ◽  
Small Cell ◽  
Primary Site ◽  
Seer Database ◽  
Significant Difference ◽  
Incidence Pattern ◽  
The Difference

518 Background: Small cell carcinoma of the gastrointestinal tract is an uncommon histology. Limited literature is available to clinicians about the incidence, distribution and prognosis of small cell carcinoma of the gastrointestinal tract (SCGIT). We reviewed the Survival, Epidemiology and End Result (SEER) database of National Cancer Institute to understand its epidemiology and prognosis. Methods: SEER database was reviewed for patients with histologically confirmed SCGIT (8041-45) and its variants in the GIT between 2002-2007 (all stages). Variables included were age, gender, race, primary site and disease specific survival. The incidence pattern across race, gender, and site of origin for SCGIT was investigated. Chi square test was used to assess the difference of incidence pattern. 5-yr survival rate across various sites was estimated using the Kaplan–Meier method and the difference in 5-yr survival was tested by log-rank test. If the significant difference is detected, the paired comparison was performed and the p-values were adjusted by Tukey multiple-comparison method. Results: A total of 645 patients were included. The distribution of SCGIT was: colorectal (30.08%), esophagus (22.17%), pancreas (20.16%), hepatobiliary (11.63%), stomach (9.61%) and NOS (6.63%). The incidence pattern of SCGIT in males and female was significantly different (p < 0.0008). Males had a higher incidence of esophagus; stomach and pancreas while females had a higher incidence of hepatobiliary, colorectal and NOS sites. Five-year survival of SCGIT was significantly associated with the primary site of disease (p = 0.03). Paired-comparison results showed that the 5-yr survival rate for patients with pancreas small cell cancer was significantly lower than patients with stomach or NOS(4.80% -pancreas vs 5.22 %-stomach and 12.81% - NOS) (p = 0.04 and p = 0.003 respectively). There was not a significant difference between other sites. Conclusions: Small cell carcinoma of the GI tract has difference in incidence patterns between genders. The 5-yr survival of patients with pancreatic small cell carcinoma is significantly lower as compared to stomach or NOS.

The expression and clinical significance of clusterin and ki67 in cervical cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16554-e16554
Author(s):  
E. Shrestha
Keyword(s):  
Cervical Cancer ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Small Cell Carcinoma ◽  
Squamous Epithelium ◽  
Small Cell ◽  
Cancer Center ◽  
Ki67 Expression ◽  
Significant Difference ◽  
Expression Rate

e16554 Background: To explore the expression pattern and clinical significance of the CLU and proliferation indices ki67 in cervical cancer. Methods: 59 cases treated at Cancer Center Sun Yat-sen University during 1989–2006 were enrolled in the study group. The relationship was analyzed for the expressions of CLU and Ki67 with clinical factors. Results: In this study positivity of CLU in cervical SCC, 10% (3/31) cases weak positive, adenocarcinoma 21% (4/19) weak positive in small cell carcinoma 11% (1/9) moderate positive. Control groups, CLU weak positive expression, 21% (3/14) CIN 2–3 and 14% (2/13) normal squamous epithelium.CLU expression found 100% (31/31) normal endocervical glands.The Ki67 in SCC 13% (4/31) cases weak positive and 5% (1/19) adenocarcinoma. All cases small cell carcinoma revealed negative. No significant difference of the CLU expression rate between normal cervical epithelium, CIN II-III and SCC (p = 0.561). No significant difference of CLU expression rate between normal endocervical gland and adenocarcinoma (p = 0.119) as well. In Ki67, there was no significant difference of Ki67 rates between CIN 2–3 and normal squamous epithelium (p = 0.585). No significant difference of Ki67 expression rates between adenocarcinoma and normal squamous epithelium (p = 0.341). The expression of CLU and Ki67 had no correlation with FIGO stage, SCC antigen level, grade of differentiation, deep stromal invasion, and lymph node metastasis. Finally, the expression of CLU and Ki67 was not related to the 5-years DFS rates, and CLU expression was not correlated with Ki67 expression (rs = 0.500, p = 0.391). Conclusions: CLU and Ki67 was in lower rates in cervical cancer, and was not associated with any clinicopathological features. It is suggested that CLU and Ki67 have no distinct role in carcinogenesis. The further larger studies are needed to verify the results of this study. No significant financial relationships to disclose.

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