Intratumoral heterogeneity of ERBB2/HER2 expression in micropapillary urothelial carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 383-383 ◽  
Author(s):  
Sumit Isharwal ◽  
Hongying Huang ◽  
Gouri Nanjangud ◽  
Francois Audenet ◽  
Yingbei Chen ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Stage ◽  
Intratumoral Heterogeneity ◽  
Lymph Node Status ◽  
Her2 Overexpression ◽  
Strongly Correlated ◽  
Her2 Expression ◽  
The Status ◽  
Urothelial Tumors ◽  
Erbb2 Amplification

383 Background: Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. Histologically, most of these tumors are associated with variable amounts of “not otherwise specified (NOS)” urothelial carcinoma. MPUC has been shown to be associated with ERBB2/HER2 amplification and protein overexpression. However, the status and distribution of these findings within the different components of tumors containing both MP and NOS urothelial carcinoma have not been addressed. Methods: We identified 44 cases of MPUC that had tissue available for FISH and IHC at our institute, of which an NOS component sufficient for both FISH and IHC was identified in 37 cases. We followed the updated ASCO/CAP Guidelines for breast cancer and as such amplification was defined by a HER2/CEP17 ratio of ≥ 2.0 or > 6 copies of the gene and HER2 overexpression was considered with IHC scores of 2+ and 3+. Results: In urothelial tumors with both MP and NOS components (n = 37), ERBB2 amplification in MP and NOS components was present in 25 and 16 cases respectively. ERBB2 amplification was significantly higher in the MP component compared to NOS component within the same tumor (67.57% vs. 43.24%, p = 0.049). HER2 overexpression in MP and NOS components was present in 25 and 13 cases respectively. HER2 overexpression was significantly higher in the MP component compared to NOS component within the same tumor (67.56% vs. 35.13%, p = 0.012). In addition, ERBB2 amplification strongly correlated with HER2 overexpression in both MP (rho = 0.65, p < 0.001) and NOS (rho = 0.74, p < 0.001) components. In this cohort (n = 44), tumor stage and lymph node status were significant predictors for overall survival (p = 0.01, < 0.001 respectively). However, ERBB2 amplification and HER2 overexpression in MP component were not associated with patients’ survival outcome (p = 1.00, 0.75 respectively). Conclusions: In MPUC, ERBB2 amplification and HER2 overexpression were preferentially but not exclusively identified in MP component compared to NOS component within the same tumor. Our findings provide evidence for intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC.

scholarly journals Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma

2018 ◽  
Vol 77 ◽  
pp. 63-69 ◽  
Author(s):  
Sumit Isharwal ◽  
Hongying Huang ◽  
Gouri Nanjangud ◽  
François Audenet ◽  
Ying-Bei Chen ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Intratumoral Heterogeneity ◽  
Her2 Expression ◽  
Erbb2 Amplification

scholarly journals MP48-03 INTRATUMORAL HETEROGENEITY OF ERBB2 AMPLIFICATION AND HER2 EXPRESSION IN MICROPAPILLARY UROTHELIAL CARCINOMA

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Sumit Isharwal ◽  
Hongying Huang ◽  
Gouri Nanjangud ◽  
François Audenet ◽  
Ying-Bei Chen ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Intratumoral Heterogeneity ◽  
Her2 Expression ◽  
Erbb2 Amplification

HER2 status of patients with invasive breast cancer in a population at a single UK centre: Correlation with tumor characteristics

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11094-11094
Author(s):  
B. Saleh ◽  
S. Jader ◽  
J. Singer ◽  
S. Jenkins ◽  
H. Bradpiece ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Invasive Breast Cancer ◽  
Age Groups ◽  
Her2 Status ◽  
Lymph Node Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Node Negative

11094 Background: The human epidermal growth factor receptor 2 (HER2) overexpression, has been correlated with higher histological grade, increased tumour size, positive lymph node status, and negative or lower oestrogen receptor (ER) expression. Our aim was to look at the association between HER2 status, patient age and tumour histopathologic characteristics. Methods: We analysed retrospectively 735 cases of invasive breast cancer treated between the years 2000 and 2004. HER2 was measured by immunohistochemistry (IHC) and all IHC 2+ tumours were also tested by fluorescent in situ hybridisation (FISH). All information was collected from pathology reports in patient case records. Results: A total of 143 (19.5%) tumours were HER2 positive (120 IHC 3+ and 23 IHC 2+/FISH+). Of the 66 tumours that were IHC 2+, 23 (34.8%) were FISH-positive. The age of most patients (75.8%) was over 50 years but there was a higher incidence (28%) of HER2 overexpresion in the 40–49 age group compared to all other age groups, the incidence of HER2 overexpression was still at least 17–18% in all age groups, including patients aged =70 years. Although, a high proportion of patients (62.2%) had tumours less than 2 cm in size, comparison of tumours less than 2 cm with those greater than 2 cm showed no predictive effect of size on HER2 expression. Over half of the patients had lymph node-negative disease (55.2%) and despite some association of HER2 expression with lymph node involvement (odds ratio of 1.23 for comparison of lymph node-positive versus negative), 19% of lymph node-negative tumours overexpressed HER2. Most tumours were high grade (32.8% grade 3, 44.1% grade 2 ) and although the proportion of HER2 overexpression increased with increasing tumour grade, some grade 1 tumours still overexpressed HER2. A higher proportion (28%) of ER-negative tumours was HER2 positive compared to ER-positive tumours (18%); however, co-expression of HER2 and ER occurred in 14% (105/735) of all primary cancers. Conclusions: In conclusion, it is not possible to predict which patients will be HER2 positive. Therefore, it is essential that HER2 status should be determined in all patients with invasive breast cancer to allow a decision on the use of trastuzumab and guide the choice of chemotherapy. No significant financial relationships to disclose.

scholarly journals Abnormal FHIT gene transcript and c-myc and c-erbB2 amplification in breast cancer.

2002 ◽  
Vol 49 (2) ◽  
pp. 341-350 ◽  
Author(s):  
Renata Kowara ◽  
Filip Gołebiowski ◽  
Paweł Chrzan ◽  
Jaroslaw Skokowski ◽  
Andrzej Karmolinski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Positive Lymph Node ◽  
Lymph Node Status ◽  
Gene Transcript ◽  
Western Blots ◽  
Fhit Gene ◽  
The Status ◽  
Gene Transcripts ◽  
Fhit Protein ◽  
Erbb2 Amplification

Searching for ways to improve the characterization of breast cancer we examined the relationship between the status of the FHIT gene transcript and amplification of c-myc and the c-erbB2 oncogene. Abnormal FHIT transcript was detected in 32 of 79 cancers examined. The presence of Fhit protein estimated by Western blots was evident only in cancers exhibiting a normal-sized FHIT transcript. This indicates that abnormal FHIT transcripts observed in our study did not encode any Fhit protein or the amount of such protein was very low. There was no association between the presence of aberrant FHIT gene transcript with age, tumor size, estrogen and progesterone receptor status, local metastases and histological grading. However, the abnormalities in FHIT gene transcripts were observed with different frequency depending on the histopathological type of the tumor. The aberrant FHIT transcript was detected in 60% of lobular cancers and only in 28% of ductal cancers. Analyzing the occurrence of c-myc and c-erbB2 amplification and the presence of aberrant FHIT gene transcripts we found that the aberrant FHIT transcript more frequently occurred in tissues with c-myc amplification. There was a significant (P < 0.05) correlation between the occurrence of the aberrant FHIT gene transcript with accompanying c-myc amplification and positive lymph node status. However, in order to evaluate the predictive value of these findings in breast cancer, an extended clinical follow up will be necessary.

Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar immune microenvironment as compared to conventional UC.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 477-477
Author(s):  
Myriam Kossai ◽  
Camélia Radulescu ◽  
Julien Adam ◽  
Anaïs Dziegielewski ◽  
Nicolas Signolle ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Clinicopathological Characteristics ◽  
Control Group ◽  
Histopathological Analysis ◽  
Her2 Overexpression ◽  
Cd8 Cells ◽  
Chemotherapeutic Sensitivity ◽  
Pathological Variant ◽  
Lower Expression

477 Background:Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated. Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n = 32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n = 30). Methods: Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8+ lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated. Clinical data were collected. Results: Plasmacytoid UC expressed GATA3 (97% vs 86% p = 0.18), CK20 (59% vs 36% p = 0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, p < 0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, p < 0.05) and p63 (41% vs 80%, p < 0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (p = 0.5). PD-L1 expression on IC was similar compared to conventional UC (p = 0.3). Overall survival at 5 years was significantly lower among patients with plasmacytoid UC compared to patients with conventional UC (p = 0.02). Conclusions: Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.

The Status Quo of Sustainable Tourism Development in Phuket. A Qualitative Assessment

2021 ◽  
Vol 12 (1) ◽  
pp. 167
Author(s):  
Kevin FUCHS ◽  
Kris SINCHAROENKUL
Keyword(s):  
Sustainable Tourism ◽  
Status Quo ◽  
Qualitative Assessment ◽  
Strongly Correlated ◽  
Structured Interviews ◽  
Sustainable Tourism Development ◽  
Mass Tourism ◽  
Current State ◽  
The Status ◽  
Coherent Leadership

Sustainable tourism is an increasingly fashionable term that is strongly correlated with the global age of increased mobility. While there is increasing interest in sustainable tourism, there is no contemporary research that describes the current state of Phuket, Thailand, the mass-tourism destination. An in-depth review of existing literature revealed that sustainable tourism at large receives a great deal of attention in its current state. This paper aimed to go beyond the common theme of sustainable tourism and conducted a thorough analysis about the status quo in Phuket with regard to sustainable tourism. Qualitative data was collected through semi-structured interviews (n=5) with industry experts and later analyzed the content by the means of thematic analysis. The research is specific to Phuket; therefore, the results of this research are not generalizable to other mass-tourism locations. There is no one-size-fits-all solution, but it is evident that stakeholders in Phuket recognize the importance of sustainable tourism. Moreover, the lack of accountability, coherent leadership, and consistency resulted in a high failure rate when initiatives were launched to improve sustainable tourism behavior in Phuket.  

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Kai Gan ◽  
Yue Gao ◽  
KuangZheng Liu ◽  
Bin Xu ◽  
Ming Chen
Keyword(s):  
Bladder Cancer ◽  
Clinical Significance ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Tumor Stage ◽  
The Cancer Genome Atlas ◽  
Her2 Expression ◽  
Large Tumor ◽  
Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

scholarly journals Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells

2020 ◽  
Vol 98 (4) ◽  
pp. 355-367 ◽  
Author(s):  
Alessandro Nini ◽  
Michèle Janine Hoffmann ◽  
Rita Lampignano ◽  
Robert große Siemer ◽  
Guus Dalum ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Carcinoma Cells ◽  
Her2 Expression

Evaluation of Chromogranin a Expression in Serum and Tissues of Breast Cancer Patients

2001 ◽  
Vol 16 (4) ◽  
pp. 268-272 ◽  
Author(s):  
L. Giovanella ◽  
M. Marelli ◽  
L. Ceriani ◽  
G. Giardina ◽  
S. Garancini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chromogranin A ◽  
Neuroendocrine Differentiation ◽  
Serum Levels ◽  
Tumor Stage ◽  
Lymph Node Status ◽  
Ca 15.3 ◽  
Tumor Histology ◽  
The Relationship ◽  
Extent Of Disease

Human chromogranin A (CgA) is a member of the granin family and is widely distributed in large dense core granules of endocrine and neuroendocrine cells. A variety of non-neuroendocrine carcinomas arising in various tissues show patterns of neuroendocrine differentiation. Expression of CgA has been documented in epithelial cells of normal mammary gland as well as in breast cancers, and elevation of serum CgA has been detected in patients with breast cancer. Our study was undertaken to evaluate the relationship between serum CgA levels and neuroendocrine features in breast cancer. In addition, we evaluated the expression of serum CgA in patients affected by breast cancer compared to controls and the relationship between serum CgA and tumor histology, extent of disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266 patients with infiltrating ductal or lobular breast carcinoma and a group of 100 age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3 was 0.06 and 0.34, respectively (χ219.1, p<0.0005). No relationship was found between serum levels of CgA and tumor histology, extent of disease, lymph node status or tumor stage while serum levels of CA 15.3 were strongly correlated with all these variables but tumor histology. No relationship was found between serum levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA-negative patients and was negative in all cases. We also evaluated eight cases of pathologically-proven neuroendocrine breast cancer: only four and two of these showed positive CgA immunostaining and increased serum CgA concentration, respectively. In conclusion, serum CgA assay offers no additional information regarding the presence, the extent and the histology of breast cancer compared to the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or exclude the rare neuroendocrine differentiation of breast cancer. We therefore conclude that CgA is not useful as a serum marker in breast cancer.

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