Reduced Expression of Claudin-2 is Associated with High Histological Grade and Metastasis of Feline Mammary Carcinomas

2014 ◽  
Vol 150 (2-3) ◽  
pp. 169-174 ◽  
Author(s):  
A.R. Flores ◽  
A. Rêma ◽  
F. Carvalho ◽  
A. Faustino ◽  
P. Dias Pereira
Keyword(s):  
Histological Grade ◽  
High Histological Grade ◽  
Mammary Carcinomas

scholarly journals Activation of Signal Transducer and Activator of Transcription 5 in Human Prostate Cancer Is Associated with High Histological Grade

2004 ◽  
Vol 64 (14) ◽  
pp. 4774-4782 ◽  
Author(s):  
Hongzhen Li ◽  
Tommi J. Ahonen ◽  
Kalle Alanen ◽  
Jianwu Xie ◽  
Matthew J. LeBaron ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histological Grade ◽  
Human Prostate ◽  
Signal Transducer ◽  
Human Prostate Cancer ◽  
High Histological Grade

p63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma

2020 ◽  
pp. jclinpath-2020-206643
Author(s):  
Shuangping Guo ◽  
Yingmei Wang ◽  
Joseph Rohr ◽  
Li Shang ◽  
Jing Ma
Keyword(s):  
Breast Carcinoma ◽  
Neoadjuvant Therapy ◽  
Histological Grade ◽  
Clinicopathological Features ◽  
Breast Carcinomas ◽  
Her2 Positive ◽  
P53 Expression ◽  
High Histological Grade ◽  
Younger Age ◽  
Significant Difference

Aimp63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association with clinicopathological features of human epidermal growth factor receptor 2 (HER 2)-positive breast carcinoma is poorly investigated.Materials and methodsSixty-seven patients with oestrogen receptor-negative and progesterone receptor-negative, HER2-positive breast carcinoma who received anti-HER2-based neoadjuvant±adjuvant therapy was retrospectively analysed.ResultsTwenty cases were p63-positive and 47 cases were p63-negative. The clinicopathological features and tumour responses after neoadjuvant therapy and outcomes were analysed. Among HER2-positive tumours, expression of p63 was significantly associated with younger age (42.5 vs 55.9; p=0.010). Expression of p63 was also significantly associated with histological grade 3 (11/20 (55%) vs 11/47 (23.4%); p=0.012) and negatively associated with grade 2 (9/20 (45%) vs 36/47 (76.6%); p=0.012). Intriguingly, p63-positive breast carcinomas showed significant aberrant p53 expression by immunohistochemistry (16/18 (88.9%) vs 29/47 (61.7%); p=0.03) and of TP53 mutation by Sanger sequencing (15/16 (93.8%) vs 12/22 (54.5%); p=0.009). No significant difference in tumour response after anti-HER2 neoadjuvant therapy nor in survival were found between p63-positive and p63-negative breast carcinomas.ConclusionExpression of p63 in HER2-positive breast carcinoma is significantly associated with younger age, poor differentiation, high histological grade and aberrant expression of p53 and of TP53 mutation. HER2-positive breast carcinoma with a myoepithelial immunophenotype shows distinctive clinicopathological features representing a distinct subtype of HER2-positive breast carcinoma. Further, these findings suggest an interaction between p63 and mutant p53 in the tumorigenesis of HER2-positive breast carcinomas.

scholarly journals Feline Invasive Mammary Carcinomas: Prognostic Value of Histological Grading

2019 ◽  
Vol 56 (5) ◽  
pp. 660-670 ◽  
Author(s):  
Elie Dagher ◽  
Jérôme Abadie ◽  
Delphine Loussouarn ◽  
Mario Campone ◽  
Frédérique Nguyen
Keyword(s):  
Prognostic Value ◽  
Malignant Tumors ◽  
Histological Grade ◽  
Grading System ◽  
Human Breast ◽  
Histological Grading ◽  
Cancer Specific Survival ◽  
Mammary Carcinomas ◽  
Histologic Grading ◽  
Grading Systems

Feline mammary carcinomas are highly malignant tumors usually associated with poor outcome. Nevertheless, survival times can differ significantly according to various prognostic factors. The Elston and Ellis (EE) histologic grading system, originally developed for human breast cancer, is commonly used to grade feline mammary carcinomas, although it is not really adapted for this species, hence the need of a more relevant grading system. Although few veterinary studies attempted to validate previously published results in an independent cohort, the aim of our study was to evaluate the prognostic value of different histologic grading systems in feline invasive mammary carcinomas, including the EE grading system applicable to human breast cancers and the modified and newly designed histologic grading systems recently proposed by Mills et al. Survey data and histologic features of 342 feline invasive mammary carcinomas were analyzed with respect to overall and cancer-specific survival. The histological grading system with best prognostic value was the mitotic-modified Elston and Ellis (MMEE) grading system: grade III carcinomas ( P = .04, hazard ratio [HR] = 1.46, 95% CI, 1.01–2.11), grade II ( P = .03, HR = 1.39, 95% CI, 1.03–1.88), and grade I carcinomas (HR = 1.00, reference), with decreasing hazard ratios significantly were associated with a worse overall survival, independently from the pathologic tumor size (pT ≥ 20 mm: P = .002, HR = 1.45, 95% CI, 1.15–1.83) and positive nodal stage ( P = .001, HR = 1.51, 95% CI, 1.18–1.94). This retrospective study validates Mills et al’s proposal to adapt the thresholds for mitotic counts to better assess the histological grade of the highly proliferative mammary carcinomas encountered in the cat.

scholarly journals Prognostic Factors in Canine Mammary Carcinomas and HER2 Expression Relationship

2017 ◽  
Vol 45 (1) ◽  
pp. 9 ◽  
Author(s):  
Nicolle Pereira Soares ◽  
Alessandra Aparecida Medeiros ◽  
Igor De Paula Castro ◽  
Taís Meziara Wilson ◽  
Taís De Almeida Moreira ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Histological Grade ◽  
Her2 Expression ◽  
Mammary Carcinomas ◽  
Node Metastasis ◽  
In Situ Carcinoma ◽  
Grade Iii

Background: The human epidermal growth factor type 2 (HER2) receptor is a membrane glycoprotein tyrosine kinase. In woman, HER2 expression is diagnosed in 30% of breast carcinomas and it is associated with a worse prognosis, higher rate of recurrence and mortality. In the bitch, the HER2 overexpression in canine mammary tumors is still controversial and the prognostic value remains uncertain. Thus, we aimed to verify the HER2 expression in canine mammary carcinomas and relate it to the type and histological grade, lymph node metastasis and clinical staging.Materials, Methods & Results: Ninety bitches diagnosed with mammary carcinoma were included in this study. The inclusion criteria were bitches with complete clinical examination, thoracic radiographic examination and submitted unilateral or bilateral mastectomy. Ninety-nine samples of mammary carcinoma were used and the fragments of tumor and regional lymph nodes were fixed in 10% neutral formalin for histopathological and immunohistochemistry analysis. The lesions were evaluated by two pathologists and classified according to the type and histological grade. HER2 expression was performed by semi-quantitative analysis of the slides according to the HerceptTestTM (Dako) recommended score. Simple carcinomas were the most frequent (51.51%) followed by complex carcinomas (46.47%) and in situ carcinoma (2.02%). The histological grade of 97 carcinoma samples was attributed, except in situ carcinoma, 37 (38.14%) of the neoplasms were grade I, 50 (51.55%) grade II and only 10 (10.31%) tumors were classified as grade III. Forty bitches were submitted to clinical staging (TNM) and 42.50% of the bitches received staging in grade I and, 25% of the bitches staged in grade IV and V, with metastases. The HER2 expression, 13/99 samples (13.13%) received score +2, 19/99 (19.19%) score +1 and absence of marking (score 0) was identified in 67 samples (67.80 %). Immunostaining in hyperplastic or normal epithelial cells was evidenced, often in association with weak or moderate cytoplasmic labeling. Of the samples expressing +2 score for HER2 (n = 13), eight samples (17.39%) were complex carcinoma and five (9.80%) simple carcinomas. There was no relationship between HER2 immunostaining with age, tumor size, TNM, histological type, histological gradation, lymph node metastasis and distance. Animals with lymph node metastasis, as well as those diagnosed with distant metastasis, did not present HER2 expression in the tumors.Discussion: The simple carcinoma seems to be the most frequent type histological diagnosed in canine mammary carcinomas, followed by carcinoma in mixed tumor and complex carcinoma. Tubulopapillary carcinomas are more invasive in the female dogs as well as in the woman. Carcinomas grade I and II are more frequent and present a better prognosis for the dog. However, bitches with grade III carcinoma survived for a shorter time when compared to dogs with grade I or II tumors. A factor that may have contributed to the lower number of bitches at worst prognostic stage (EC IV and V) is the current owners’ awareness that they have sought veterinary help earlier, as soon as they detect small nodules in mammary gland. Overexpression of HER2 in women breast cancer is diagnosed in 20-30% of cases, whereas in bitches, this expression is variable. Also the different percentages of canine HER2 immunostaining are due to the lack of standardization for the analysis of the immunostaining, the immunohistochemical techniques employed and the non-specificity of the HER2 antibody. In canine mammary carcinomas the HER2 expression in low and this immunostaining is not related to other established prognostic factors. This study reinforces the hypothesis put forward by other authors that in the bitch the expression of HER2 may not be related to malignancy and tumor progression.

scholarly journals Unfavorable Prognostic Effects of the Stem Cell Pluripotency Factor Sox2 in Feline Invasive Mammary Carcinomas

2021 ◽  
Vol 7 ◽  
Author(s):  
Yohan Truchot ◽  
Elie Dagher ◽  
Jérôme Abadie ◽  
Frédérique Nguyen
Keyword(s):  
Estrogen Receptor Alpha ◽  
Histological Grade ◽  
Clinical Stage ◽  
Growth Factor Receptor ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Cancer Specific Survival ◽  
Ki 67 ◽  
Mammary Carcinomas ◽  
Sox2 Expression

Background: Sex-determining Region Y (SRY)-box transcription factor-2 (Sox2) belongs to the “Yamanaka's factors,” necessary and sufficient to convert somatic cells into pluripotent stem cells. In breast cancers, Sox2 expression has been associated with poor prognosis, and resistance to therapy. The aims of this study were to determine the frequency of Sox2 positivity in feline invasive mammary carcinomas (FMCs), its relationships with other clinical-pathologic variables, and with patient outcomes.Materials and Methods: This study relies on a previously described retrospective cohort of 180 FMCs, diagnosed in female cats treated by mastectomy alone, with 2-year follow-up. Sox2 (clone SP76), Estrogen Receptor alpha (ER), Progesterone Receptor (PR), Ki-67, Human Epidermal growth factor Receptor 2 (HER2), Androgen Receptor (AR), Bcl-2, Forkhead box protein A1 (FOXA1), basal markers and FoxP3-positive regulatory T cells (Tregs) were detected by automated immunohistochemistry. Sox2 expression was quantitated as an index (percentage of neoplastic cells demonstrating a positive nuclear signal). The FMCs were considered Sox2-positive at threshold >42%.Results: Sox2 was not expressed in the normal mammary gland or in mammary hyperplasia without atypia, but was occasionally detected in atypical hyperplasia. In FMCs, the mean Sox2 index was 38 ± 30%, and 79/180 FMCs (44%) were Sox2-positive. Sox2 expression was associated with older age at diagnosis, lymphovascular invasion, high Ki-67 proliferation indexes, low PR and FOXA1 expression, and increased numbers of tumor-associated Tregs, but was not significantly associated with the clinical stage, histological types, and histological grade. By multivariate survival analysis, Sox2 was associated with poor cancer-specific survival (Hazard Ratio = 1.48, 95% confidence interval 1.04–2.11, p = 0.0292), independently of the pathologic tumor size, pathologic nodal stage, distant metastasis, and AR expression. A rare subgroup of FMCs characterized by an AR+Sox2–phenotype (19/180 cases, 11%) was associated with very favorable outcomes.Conclusion: Sox2 expression was associated with poor cancer-specific survival of female cats with invasive mammary carcinomas, as previously reported in human breast cancer, but was more commonly expressed in cats than reported in breast cancers. Sox2 showed complementarity with AR in FMC prognostication.

WITH SURGICAL REMOVAL OR ADJUVANT CHEMOTHERAPY INCREASE THE TWO-YEAR SURVIVAL AND ASSOCIATED CLINICOPATHOLOGIC FACTORS IN CATS WITH MAMMARY CARCINOMAS

2019 ◽  
Vol 45 (03) ◽  
pp. 57-66
Author(s):  
Ti-Yun Lo ◽  
Yu-Ching Feng ◽  
Yi-Ping Yang ◽  
Jiunn-Wang Liao ◽  
Shih-Chieh Chang
Keyword(s):  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Histological Grade ◽  
Biological Behavior ◽  
Prognostic Indicators ◽  
Surgical Removal ◽  
Mammary Carcinomas ◽  
Clinicopathologic Factors ◽  
Advanced Stages ◽  
One Year

Due to the aggressive biological behavior, a large number of studies attempt to identify the prognostic indicators for feline mammary carcinoma (FMC). In this study, we retrospectively identified the prognostic indicators and evaluated the effect of surgery with or without adjuvant chemotherapy on 47 cats with FMCs. Over a two-year follow-up period, surgical removal was significantly associated with greater overall survival time (OST). In cats that underwent surgical treatment, median OST was longer in cats that underwent surgery with adjuvant chemotherapy (540 days) than cats that underwent surgery without chemotherapy (398 days). In addition, cats with FMCs in early stage (I or II) had longer OST than cats in advanced stages. Further, through multivariate analyses, the histological grade was found to be significantly associated with a survival of two years. Cats with FMCs at high grade were most likely to have a mean or median OST of less than one year. In summary, stage, grade and the size of tumor were all prognostic factors, in which histological grade was found to be the only significant factor in cats with mammary carcinomas through multivariate analysis.

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