CD44 and CD24 Expression and Prognostic Significance in Canine Mammary Tumors

CD44+/CD24– phenotype has been used to identify human and canine mammary cancer stem-like cells. In canine mammary tumors, CD44+/CD24– phenotype has been associated with high grade and lymph node infiltration. However, several studies have reported opposing results regarding the clinical significance of phenotypic groups formed by the combination of CD44 and CD24 in both human and canine mammary tumors. So far, no study has investigated the correlation between these phenotypes and survival in dogs. The aim of this study was to investigate the expression and distribution of CD44 and CD24 in canine mammary carcinomas and to correlate them with histological diagnosis and survival in a well-characterized cohort. Immunohistochemistry was performed in 96 mammary carcinomas with antibodies against CD44 and CD24. Expression of CD44+ and CD44+/CD24– phenotype was detected in 75 of 96 (78%) and 63 of 96 (65.6%) carcinomas, respectively. Their expression was associated with tumor type, occurring more often in tubular complex carcinomas than in solid carcinomas. CD44+/CD24– phenotype was associated with a better overall survival ( P = .001). CD24+ expression was detected in 52 of 96 tumors (54%) and CD44–/CD24+ phenotype in 39 of 96 tumors (40.6%). Both were associated with poor clinicopathological parameters (high grade, and emboli). No correlation with overall survival was observed. CD44+/CD24– expression was associated with a better prognosis and occurred at high frequency and high level, indicating that this phenotype is not suitable to detect cancer stem cells in canine mammary carcinomas. Although further studies are needed, our results suggest that CD24 may constitute a valuable marker of poor prognosis for canine mammary carcinomas.

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Expression and Prognostic Significance of Neurotrophins and Their Receptors in Canine Mammary Tumors

Veterinary Pathology ◽

10.1177/0300985820921813 ◽

2020 ◽

Vol 57 (4) ◽

pp. 507-519

Author(s):

Bernadette Rogez ◽

Quentin Pascal ◽

Audrey Bobillier ◽

François Machuron ◽

Robert-Alain Toillon ◽

...

Keyword(s):

Biological Effects ◽

Prognostic Significance ◽

Mammary Tumors ◽

Clinicopathological Parameters ◽

Lymph Node Status ◽

Mammary Carcinomas ◽

Canine Mammary Tumors ◽

Common Receptor ◽

Specific Receptors

Accumulating data highlight the role of neurotrophins and their receptors in human breast cancer. This family includes nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both synthetized as proneurotrophins (proNGF and proBDNF). (pro)NGF and (pro)BDNF initiate their biological effects by binding to both their specific receptors TrkA and TrkB, respectively, and the common receptor p75NTR. Currently, no data are available about their expression and potential role in canine mammary tumors. The aim of this study was to investigate expression of proNGF and BDNF as well as their receptors TrkA, TrkB, and p75NTR in canine mammary carcinomas, and to correlate them with clinicopathological parameters (grade, histological type, lymph node status, recurrence, and distant metastasis) and survival. Immunohistochemistry was performed on serial sections of 96 canine mammary carcinomas with antibodies against proNGF, BDNF, TrkA, TrkB, and p75NTR. Of the 96 carcinomas, proNGF expression was detected in 71 (74%), BDNF in 79 (82%), TrkA in 94 (98%), TrkB in 35 (37%), and p75NTR in 44 (46%). No association was observed between proNGF, BDNF, or TrkA expression and either clinicopathological parameters or survival. TrkB and p75NTR expression were associated with favorable clinicopathological parameters as well as better overall survival.

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Involvement of Nestin in the Progression of Canine Mammary Carcinoma

Veterinary Pathology ◽

10.1177/03009858211018656 ◽

2021 ◽

pp. 030098582110186

Author(s):

Hisashi Yoshimura ◽

Maiko Moriya ◽

Ayaka Yoshida ◽

Masami Yamamoto ◽

Yukino Machida ◽

...

Keyword(s):

Epithelial Cells ◽

Mammary Carcinoma ◽

Mammary Tumors ◽

Carcinoma Cells ◽

Nestin Expression ◽

Mammary Carcinomas ◽

Canine Mammary Carcinoma ◽

Canine Mammary Tumors ◽

Mammary Carcinoma Cells ◽

Luminal Epithelial Cells

Nestin, a class VI intermediate filament protein, is known to be expressed in various types of human neoplasms, including breast cancer, and is associated with their progression. However, its expression and role in canine mammary tumors remain unknown. We analyzed nestin expression in canine mammary tumors using in situ hybridization and immunohistochemistry. We also investigated its role in a canine mammary carcinoma cell line using RNA interference. Nestin expression was not observed in luminal epithelial cells of any of the 62 cases of benign mammary lesions examined, although myoepithelial cells showed its expression in most cases. In 16/50 (32%) primary mammary carcinomas and 6/15 (40%) metastases of mammary carcinomas, cytoplasmic nestin expression was detected in luminal epithelial cells. In luminal cells of primary mammary carcinomas, its expression was positively related to several pathological parameters that indicate high-grade malignancy, including histological grading ( P < .01), vascular/lymphatic invasion ( P < .01), Ki-67 index ( P < .01), and metastasis ( P < .05). Immunohistochemistry revealed that nestin expression was related to vimentin expression in mammary carcinomas ( P < .01). This relationship was confirmed using reverse transcription-quantitative polymerase chain reaction using 9 cell lines derived from canine mammary carcinoma ( P < .01). Finally, nestin knockdown in canine mammary carcinoma cells using small interfering RNA inhibited cell proliferation and migration based on WST-8, Boyden chamber, and cell-tracking assays. These findings suggest that nestin may at least partially mediate these behaviors of canine mammary carcinoma cells.

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Differential Characteristics and Prognosis of PD-L1–Positive Endometrial Carcinomas: A Retrospective Chart Review

Life ◽

10.3390/life11101047 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1047

Author(s):

Justin Z. Amarin ◽

Razan Mansour ◽

Sura Al-Ghnimat ◽

Maysa Al-Hussaini

Keyword(s):

Overall Survival ◽

Tumor Cells ◽

Chart Review ◽

Prognostic Significance ◽

Retrospective Chart Review ◽

Cancer Center ◽

High Grade ◽

Endometrial Carcinomas

Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PDL1–positive endometrial carcinomas and the prognostic significance of PDL1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007–2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PDL1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PDL1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PDL1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.

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Expression of Apoptotic Protease Activating Factor-1 in adenoid cystic carcinoma of the salivary glands and its clinicopathological relevance

Vojnosanitetski pregled ◽

10.2298/vsp201026130d ◽

2020 ◽

pp. 130-130

Author(s):

Branko Dozic ◽

Boban Anicic ◽

Vladimir Sinobad ◽

Nikola Mikovic ◽

Srdjan Milanovic ◽

...

Keyword(s):

Overall Survival ◽

Salivary Glands ◽

Tumor Cells ◽

Statistical Significance ◽

Clinicopathological Parameters ◽

Tumor Type ◽

Immunohistochemical Expression ◽

Apoptosis Pathway ◽

Intrinsic Apoptosis Pathway ◽

Histological Tumor Type

Background/Aim. Apoptotic Protease Activating Factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis. Some pathological conditions such as cancer, stroke, and neurodegenerative diseases, are the result of disregulation in the intrinsic apoptosis pathway. The aim of this study was to analyse the immunohistochemical expression of Apaf-1 in ACC tumor cells of the salivary glands and its correlation with clinicopathological parameters (gender, age, localization, histological type and overall survival). Methods. Formalin-fixed, paraffin-embedded tissues from 50 human ACC of the salivary glands, male and female, average age 58 years, were used for our present study. We used the technique of tissue microarray (TMA blocks). Sections from the TMA mould, 5?m thick, were stained with the streptavidin-biotin immunohistochemical technique using primary antibodies specific for Apaf-1 (Leica Biosystems, Newcastle, UK). Stained tissue sections were analyzed by the light microscope (Olympus type BH-2). Based on the data collected, the database was created in SPSS software v. 22.0 (SPSS Inc., Chicago, ILL, USA), which was used for a further statistical analysis. The statistical data analysis included methods of descriptive and analytical (inferential) statistics. Results. The results of the immunohistochemical analysis of Apaf-1 expression in the samples of patients with ACC of the salivary glands were compared with the clinicopathological parameters of these patients. The immunohistochemical expression of Apaf-1 showed no statistical significance with regard to the patients gender (p=0.552), age (p=0.106), histological tumor type (p=0.654) and localization of ACC in the salivary glands (p=0.486). There was no statistically significant correlation observed between overall survival of ACC patients and Apaf-1 expression in tumor cells (p=0.340,Long-Rank test). Conclusion. With regard to ACC, Apaf-1 expression is not in correlation with clinicopathological parameters (gender, age, localization, histological tumor type, outcome of the disease, and overall survival). Therefore, we believe Apaf-1 cannot be regarded as an independent prognostic factor.

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Diagnostic efficacy of smear cytology and Robinson’s cytological grading of canine mammary tumors with respect to histopathology, cytomorphometry, metastases and overall survival

PLoS ONE ◽

10.1371/journal.pone.0191595 ◽

2018 ◽

Vol 13 (1) ◽

pp. e0191595 ◽

Cited By ~ 2

Author(s):

Izabella Dolka ◽

Michał Czopowicz ◽

Anna Gruk-Jurka ◽

Agata Wojtkowska ◽

Rafał Sapierzyński ◽

...

Keyword(s):

Overall Survival ◽

Mammary Tumors ◽

Diagnostic Efficacy ◽

Canine Mammary Tumors

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Prognostic and clinicopathological significance of pretreatment mean platelet volume in cancer: a meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-037614 ◽

2020 ◽

Vol 10 (10) ◽

pp. e037614

Author(s):

Xin Chen ◽

Jing Li ◽

Xunlei Zhang ◽

Yushan Liu ◽

Jindong Wu ◽

...

Keyword(s):

Overall Survival ◽

Mean Platelet Volume ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Clinicopathological Parameters ◽

Platelet Volume ◽

Poor Overall Survival ◽

Patients With Cancer ◽

Clinicopathological Significance

ObjectiveOur study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies.DesignMeta-analysis.Data sourcesRelevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE.Eligibility criteriaAll published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included.Data extraction and synthesisStudies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated.ResultsA total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07).ConclusionsPretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.

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Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis

Disease Markers ◽

10.1155/2020/2412741 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Hexin Lin ◽

Xin Zhao ◽

Lu Xia ◽

Jiabian Lian ◽

Jun You

Keyword(s):

Malignant Tumors ◽

Human Cancer ◽

Meta Analysis ◽

Univariate Analysis ◽

Prognostic Significance ◽

Cancer Prognosis ◽

High Expression ◽

Clinicopathological Parameters ◽

Malignant Neoplasms ◽

Tumor Type

Background. Chromebox protein homolog 3 (CBX3) as a member of the heterochromatin-associated protein 1 (HP1) family has been reported to be overexpressed in human cancer tissues. Numerous studies have shown the relationship between the CBX3 expression and clinicopathological factor or prognosis in malignant tumors, but their results are inconsistent. To address these results, a meta-analysis was described to investigate the prognostic value and clinicopathological significance of CBX3 expression in human malignant neoplasms. Methods. PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) were used to search eligible literatures, including publications prior to September 2019. The role of CBX3 in cancer prognosis and clinicopathological characteristics was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results. Eleven studies with 1682 cancer patients were enrolled in this meta-analysis. This analysis demonstrated that the patients’ increased CBX3 expression was significantly associated with poor overall survival (OS) (univariate analysis: HR = 1.81 , 95% CI 1.46-2.25; multivariate analysis: HR = 1.95 , 95% CI 1.63-2.34). Subgroups analysis by tumor type also indicated that high expression of CBX3 was correlated with poor OS in tongue squamous cell carcinoma ( HR = 3.31 , 95% CI 2.03-5.39), lung cancer ( HR = 1.66 , 95% CI 1.21-2.29), genitourinary cancer ( HR = 2.03 , 95% CI 1.15-3.58), and digestive cancer ( HR = 1.48 , 95% CI 1.23-1.79). For clinicopathological features, high expression of CBX3 was associated with lymph node metastasis ( OR = 2.96 , 95% CI 1.42-6.20) and lager tumor size ( OR = 1.60 , 95% CI 1.12-2.28). Conclusion. The results of this meta-analysis indicated that CBX3 expression may be a novel biomarker for predicting patient prognosis and clinicopathological parameters in multiple human cancer.

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Amyloid in Canine Mammary Tumors

Veterinary Pathology ◽

10.1177/030098588502200409 ◽

1985 ◽

Vol 22 (4) ◽

pp. 347-354 ◽

Cited By ~ 8

Author(s):

J. H. Vos ◽

E. Gruys

Keyword(s):

Epithelial Cells ◽

Mammary Tumors ◽

Histochemical Staining ◽

Amyloid Deposition ◽

Corpora Amylacea ◽

Mammary Carcinomas ◽

Canine Mammary Tumors ◽

Stromal Tissue ◽

Staining Methods ◽

Neoplastic Epithelial Cells

In canine mammary carcinomas, amyloid was present as amyloid-containing corpora amylacea and as local deposits between neoplastic epithelial cells or in stromal tissue. Histochemical staining methods revealed that this amyloid was not of the AA-type amyloid and contained tryptophan. The possible pathogenesis of this amyloid deposition is discussed.

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Immunohistologic Detection of Estrogen Receptor Alpha in Canine Mammary Tumors: Clinical and Pathologic Associations and Prognostic Significance

Veterinary Pathology ◽

10.1354/vp.37-3-239 ◽

2000 ◽

Vol 37 (3) ◽

pp. 239-247 ◽

Cited By ~ 102

Author(s):

A. Nieto ◽

L. Peña ◽

M. D. Pérez-Alenza ◽

M. A. Sánchez ◽

J. M. Flores ◽

...

Keyword(s):

Estrogen Receptor ◽

Lymph Node ◽

Prognostic Value ◽

Malignant Tumors ◽

Prognostic Significance ◽

Mammary Tumors ◽

Proliferation Index ◽

Lymph Node Status ◽

Canine Mammary Tumors

Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-α) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3–4 months. ER-α expression was higher in tumors of genitally intact and young bitches ( P < 0.01, P < 0.01) and in animals with regular estrous periods ( P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-α ( P = 0.04). Immunoexpression of ER-α decreased significantly with tumor size ( P = 0.05) and skin ulceration ( P = 0.01). Low levels of ER-α were significantly associated with lymph node involvement ( P < 0.01). Malignant tumors had lower ER-α expression than did benign tumors ( P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-α scores ( P = 0.05) in all tumors. Low ER-α levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up ( P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-α value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-α index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-α in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.

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Comprehensive analysis of the value of RAB family genes in prognosis of breast invasive carcinoma

Bioscience Reports ◽

10.1042/bsr20201103 ◽

2020 ◽

Vol 40 (5) ◽

Cited By ~ 2

Author(s):

Shitong Lin ◽

Canhui Cao ◽

Yifan Meng ◽

Ping Wu ◽

Peipei Gao ◽

...

Keyword(s):

Overall Survival ◽

Invasive Carcinoma ◽

Expression Patterns ◽

Prognostic Significance ◽

Functional Enrichment ◽

Clinicopathological Parameters ◽

Genetic Mutations ◽

Study Results ◽

Rab Family ◽

Potential Biomarkers

Abstract Purpose: Several RAB family genes have been studied extensively and proven to play pivotal roles in the occurrence and development of certain cancers. Here, we explored commonly expressed RAB family genes in humans and their prognostic significance using bioinformatics, and then identified potential biomarkers of breast invasive carcinoma (BRCA). Materials and methods: The prognostic values (overall survival) of RAB family genes in BRCA were obtained using Gene Expression Profiling Interactive Analysis (GEPIA). The expression patterns of RAB family genes and their relationships with clinicopathological parameters in BRCA were measured using the ONCOMINE and UALCAN databases, respectively. Genetic mutations and survival analysis were investigated using the cBio Cancer Genomics Portal (c-BioPortal). Interacting genes of potential biomarkers were identified using STRING, and functional enrichment analyses were performed using FunRich v3.1.3. Results: In total, 64 RAB genes were identified and analyzed in our study. Results showed that RAB1B, RAB2A, and RAB18 were up-regulated and significantly associated with poor overall survival in BRCA. Furthermore, their higher expression was positively correlated with clinicopathological parameters (e.g. cancer stage and nodal metastasis status). DNA copy number amplifications and mRNA up-regulation were the main genetic mutations, and the altered group showed significantly poorer overall survival compared with the unaltered group. Functional enrichment analysis of RAB1B, RAB2A, and RAB18 indicated they were closely involved in GTPase activity. Conclusions:RAB1B, RAB2A, and RAB18 were up-regulated and significantly correlated with poor prognosis in BRCA. Thus, they could be applied as novel biomarkers of BRCA in future studies.

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