scholarly journals Tumor-associated macrophage is correlated with survival and SOCS protein expression in canine mammary carcinoma

2018 ◽  
Vol 38 (10) ◽  
pp. 1972-1980
Author(s):  
Carlos H.C. Vieira-Filho ◽  
Stella M. Barrouin-Melo ◽  
Karine A. Damasceno ◽  
Márcio S.S. Araújo ◽  
Natalie F. Borges ◽  
...  

ABSTRACT: The inflammatory infiltrate in the tumor microenvironment, particularly in mammary tumors, has aroused great interest in oncology, to play different roles in the progression or tumor regression dependent on the types and cell subsets involved. The present study aimed to evaluate (1) the occurrence and intensity of macrophage infiltration in the mammary carcinoma microenvironment, (2) the expression of SOCS1 and SOCS3 proteins in tumor associated macrophages, (3) any association between these parameters and tumor development, as well as survival rates in female dogs. Twenty-two female dogs diagnosed as carcinoma arising in a mixed tumor (CMT) by histopathology were divided into two groups following mastectomy: dogs without metastasis (CMT(-)=11) and those with metastasis (CMT(+)=11). The following parameters were analyzed: tumor size, lymph node metastasis, clinical stage, histological grade, distribution and intensity of inflammatory infiltrate, tumor macrophage quantification by immunohistochemical analysis of SOCS1 and SOCS3 expression, and immunophenotyping of peripheral blood leukocytes by flow cytometry. Dogs with the higher proportions of macrophages in the inflammatory infiltrate (≥400/tumor) also had higher survival rates in comparison with dogs with less macrophages. Immunostaining revealed higher proportions of SOCS3-positive macrophages in dogs without lymph node metastasis, while SOCS1-positive macrophages were predominant in dogs with metastasis (p<0.05). Multivariate analysis found associations between survival rate and clinical staging (p=0.025), histological grade (p=0.007), and the expression of MHC-CI in circulating monocytes (p=0.018). Higher SOCS3 expression in activated macrophages within the inflammatory infiltrate were considered indicative of an antitumor immune response, improved clinicopathological parameters and longer survival, whereas SOCS1-related activation was associated with tumor progression, metastasis development and reduced survival in female dogs with mammary carcinomas.

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Farveen Marican Abu Backer ◽  
Nik Raihan Nik Mustapha ◽  
Nor Hayati Othman

Objective. We studied the clinicopathological parameters of adenocarcinoma arising from endocervix (ECA) and from endometrium (EMA) based on the expression of P16ink4a, P21waf1, and p27Kip1 proteins.Study Design. Immunohistochemistry was done on sections of confirmed ECA and EMA from hysterectomy specimens which have had no prior chemotherapy/radiotherapy.Results. There were 40 ECAs and 92 EMAs. The mean age of ECA was 49.82 (SD 10.29); the youngest was 30 years old and the oldest 75 years old. The mean age of EMA was 54.45 (SD 10.92); the youngest was 30 years old and the oldest was 82 years old. For ECA, the size of the tumour is significantly associated with age and with depth of infiltration. FIGO stage is associated with histological grade. p21WAF1 expression is significantly associated with infiltration of the corpus and lymph node metastasis. p27Kip1 expression is significantly associated with lymph node invasion. The presence of lymph node metastasis is strongly associated when p16INK4a and p27Kip1 expressions are analyzed in combination. For EMA, p16INK4a expression is associated with histologic grade.Conclusion. Our study shows that we could use these cell cycle markers as predictors for more aggressive subsets of adenocarcinoma of the cervix and endometrium.


2021 ◽  
Vol 9 (A) ◽  
pp. 789-797
Author(s):  
Amira Mohamed Bassam ◽  
Yousra Raafat ◽  
Ahmed Mahmoud Abd Al-Aziz ◽  
Rasha Ramadan Mostafa

BACKGROUND: Tumor budding is associated with adverse histology and is a predictor of lymph node metastasis. Human chorionic gonadotropin-beta (hCG-β) expression in non-trophoblastic tumors has been associated with aggressive behavior. AIM: Evaluation of tumor budding and hCG-β _immunohistochemical expression in colorectal carcinoma (CRC), and correlation of their expression with various clinicopathological parameters. MATERIALS AND METHODS: Immunohistochemical staining for hCG-β _was performed on paraffin-embedded sections of 60 cases of CRC. Tumors with cytoplasmic or membranous staining of more than five epithelial cell clusters were designated hCG-β _positive; otherwise, they were designated hCG-β _negative. Tumor budding was assessed in hematoxylin and eosin stained slides and was classified as; low: 0–4 buds, intermediate: 5–9 buds and high: ≥10 buds; with exclusion of pure mucoid or signet ring cell morphology cases from analysis. RESULTS: Tumor budding was low in (58.8%) of the cases, intermediate in (15.7%), and high in (25.5%). There was a statistically significant correlation between tumor budding and tumor histological grade (p = 0.011), lymph node metastasis (N) (p = 0.009), overall pathologic stage group (p = 0.009), modified Dukes’ stage (p = 0.009), lymphovascular invasion (p = 0.000), and desmoplastic reaction (p = 0.004). Positive hCG-β _alpha expression was detected in 12 (20%) of cases. There were statistically significant correlations between hCG-β _expression and each of lymphovascular invasion (p = 0.042) and tumor budding (p = 0.000). CONCLUSION: hCG-β _is a marker of aggressiveness that may have essential role in tumor invasion. Tumor budding is crucial event in tumor invasion and metastasis. Tumor budding with hCG-β _expression is a novel prognostic parameter and may represent a potential therapeutic target.


2020 ◽  
Author(s):  
Zhiling Wang ◽  
Shuo Zhang ◽  
Yifei Ma ◽  
Wenhui Li ◽  
Jiguang Tian ◽  
...  

Abstract Background: The determination of lymph node(LN) status is critical for evaluating prognosis and identifying the necessity of adjuvant therapy of endometrial cancer(EC) patients. However, the significance of systematic lymphadenectomy remains controversial. This study aimed to explore the risk factors for lymph node metastasis(LNM) in patients with EC and develop a clinically useful nomogram based on clinicopathological parameters to predict it.Methods: A total of 1517 consecutive patients who underwent staging surgery for EC were abstracted from Qilu Hospital of Shandong University. Parameters including patient-related, tumor-related, and preoperative hematologic examination-related were analyzed by univariate and multivariate logistic regression to determine the correlation with LNM. Based on the multivariate results, a nomogram was constructed and underwent further validation to predict the probability of LNM.Results: The nomogram was constructed and incorporated valuable parameters from the final multivariate model including histological type, histological grade, depth of myometrial invasion, LVSI, cervical involvement, parametrial involvement, and HGB levels. The nomogram was cross-validated internally by the 200 bootstrap sample and showed good discrimination accuracy with an AUC of 0.899.Conclusions: We developed and validated a 7-variable nomogram with a high concordance probability to predict the risk of LNM in patients with EC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiling Wang ◽  
Shuo Zhang ◽  
Yifei Ma ◽  
Wenhui Li ◽  
Jiguang Tian ◽  
...  

Abstract Background This study aimed to explore the risk factors for lymph node metastasis (LNM) in patients with endometrial cancer (EC) and develop a clinically useful nomogram based on clinicopathological parameters to predict it. Methods Clinical information of patients who underwent staging surgery for EC was abstracted from Qilu Hospital of Shandong University from January 1st, 2005 to June 31st, 2019. Parameters including patient-related, tumor-related, and preoperative hematologic examination-related were analyzed by univariate and multivariate logistic regression to determine the correlation with LNM. A nomogram based on the multivariate results was constructed and underwent internal and external validation to predict the probability of LNM. Results The overall data from the 1517 patients who met the inclusion criteria were analyzed. 105(6.29%) patients had LNM. According the univariate analysis and multivariate logistic regression analysis, LVSI is the most predictive factor for LNM, patients with positive LVSI had 13.156-fold increased risk for LNM (95%CI:6.834–25.324; P < 0.001). The nomogram was constructed and incorporated valuable parameters including histological type, histological grade, depth of myometrial invasion, LVSI, cervical involvement, parametrial involvement, and HGB levels from training set. The nomogram was cross-validated internally by the 1000 bootstrap sample and showed good discrimination accuracy. The c-index for internal and external validation of the nomogram are 0.916(95%CI:0.849–0.982) and 0.873(95%CI:0.776–0.970), respectively. Conclusions We developed and validated a 7-variable nomogram with a high concordance probability to predict the risk of LNM in patients with EC.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yuejuan Xu ◽  
Jue Sun ◽  
Jianhua Xu ◽  
Qi Li ◽  
Yuewu Guo ◽  
...  

Background. Gastric cancer (GC) is an important malignant disease around the world. Abnormalities of microRNAs (miRNAs) have been implicated in carcinogenesis of various cancers. In the present study, we examined miR-21 expression in human gastric cancer with lymph node metastasis and attempted to uncover its relationship with clinicopathologic data, especially with lymph node metastasis.Materials and Methods. The expression levels of miR-21 in the tumor specimens of GC patients were quantified by RT-PCR. The correlation between miR-21 level and multiple clinicopathological factors was then examined by Mann-Whitney test, Kaplan-Meier survival analysis, and operating characteristic (ROC) analysis.Results. The expression level of miR-21 was higher in GC patients with lymph node metastasis than in those without lymph node metastasis (P<0.05). Expression level of miR-21 was significantly correlated with histologic type, T stage, lymph node metastasis and pTNM stage. The overall survival rates in GC patients with low upregulated miR-21 expression were significantly higher than those with high upregulated miR-21 (P<0.05).Conclusion. A close association is implicated between the elevated miR-21and lymph node metastasis, which could potentially be exploited as a practical biomarker for lymph node metastasis in patients with GC.


2017 ◽  
Vol 27 (4) ◽  
pp. 748-753 ◽  
Author(s):  
Alper Karalok ◽  
Taner Turan ◽  
Derman Basaran ◽  
Osman Turkmen ◽  
Gunsu Comert Kimyon ◽  
...  

ObjectiveThe aim of this study was to evaluate the effectiveness of histological grade, depth of myometrial invasion, and tumor size to identify lymph node metastasis (LNM) in patients with endometrioid endometrial cancer (EC).MethodsA retrospective computerized database search was performed to identify patients who underwent comprehensive surgical staging for EC between January 1993 and December 2015. The inclusion criterion was endometrioid type EC limited to the uterine corpus. The associations between LNM and surgicopathological factors were evaluated by univariate and multivariate analyses.ResultsIn total, 368 patients were included. Fifty-five patients (14.9%) had LNM. Median tumor sizes were 4.5 cm (range, 0.7–13 cm) and 3.5 cm (range, 0.4–33.5 cm) in patients with and without LNM, respectively (P = 0.005). No LMN was detected in patients without myometrial invasion, whereas nodal spread was observed in 7.7% of patients with superficial myometrial invasion and in 22.6% of patients with deep myometrial invasion (P < 0.0001). Lymph node metastasis tended to be more frequent in patients with grade 3 disease compared with those with grade 1 or 2 disease (P = 0.131).ConclusionsThe risk of lymph node involvement was 30%, even in patients with the highest-risk uterine factors, that is, those who had tumors of greater than 2 cm, deep myometrial invasion, and grade 3 disease, indicating that 70% of these patients underwent unnecessary lymphatic dissection. A precise balance must be achieved between the desire to prevent unnecessary lymphadenectomy and the ability to diagnose LNM.


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 ◽  
...  

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.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5587-5587
Author(s):  
J. Park ◽  
S. Seo ◽  
S. Kang ◽  
S. Lim ◽  
M. Lim ◽  
...  

5587 Background: Previosly, we reported the accuracy of positron emission tomography with 2-[fluorine18] fluoro-2-deoxy-D- glucose (FDG-PET) for detecting metastatic lymph node (LN) in cervical cancer (Eur J Cancer 2005: 41; 2086–92). The aim of this prospective study was to evaluate the accuracy of PET/CT for detecting lymph node metastasis in cervical cancer and to compare the accuracy between PET and PET/CT. Methods: From May 2002 to Jul 2006, 86 patients with untreated stage IB-IVA cervical cancer were enrolled. All patients underwent pretreatment clinical staging including PET (May 2002-Aug 2003, 54 patients) or PET/CT (Jan 2004-Jul 2006, 32 patients) followed by surgical staging including systematic pelvic and paraaortic lymph node (PLN and PALN) dissection. To enable region specific comparisons, PALN and PLN were divided into eight regions: both PALN, both common iliac areas, both external iliac areas, and both internal iliac/obturator areas. Each lymph node was sliced at 2-mm intervals perpendicular to the greatest dimension to maximize the likelihood of detecting micrometastases. All metastatic tumor size in each involved lymph node was measured. Histopathologic evaluation of lymph nodes was the diagnostic standard. The study protocol was approved by Institutioal Review Board, and a written informed consent was obtained. Results: A total of 688 LN regions were evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of PET and PET/CT are shown in Table 1 . As the metastatic tumor size increased, the sensitivity of PET and PET/CT was improved. Although there were no differences in sensitivity for detecting large sized (> 5mm or 10mm) metastatic tumor, PET/CT was more sensitive than PET for all pathologically proven LN metastasis which included small sized (< 5mm) metastatic tumor. Conclusions: PET/CT was more sensitive than PET for detecting small sized (<5mm) lymph node metastasis in cervical cancer. [Table: see text] No significant financial relationships to disclose.


Sign in / Sign up

Export Citation Format

Share Document