scholarly journals Proliferative activity of colorectal adenocarcinoma: objectification of criteria of morphological evaluation

2018 ◽  
Vol 18 (3) ◽  
pp. 52-56
Author(s):  
D P Kovtun ◽  
N M Anichkov ◽  
O G Polushin ◽  
E V Ponomaryeva ◽  
A I Lyubimov ◽  
...  

Aim of the study. To analyze the correlation between proliferative activities determined on the basis of routine histological staining and immunohistochemical reaction to the nuclear antigen Ki-67 in colorectal adenocarcinomas. Methods. Thirty adenocarcinomas of the colon and rectum were retrospectively evaluated. Evaluation of proliferative activity was performed on serial histological preparations stained with hematoxylin and eosin and treated with antibodies to Ki-67. Calculation was carried out in the “hot spots” under four microscope high power fields (≈1 mm2). Results. An estimate of the Kendall rank correlation coefficient demonstrated a high degree of direct relationship between the number of mitoses counted by routine staining and proliferative activity estimated by the immunohistochemical method (τ = 0.708, p < 0.05). All observations on the dispersion diagram could be divided into three “cloud” clusters with similar values for Ki-67 with practically the same number of mitoses. Conclusions. On the basis of routine histological examination, it is possible to separate colorectal carcinomas from tumors with a low (1-2/mm2), moderate (3-5/mm2), and high (≥6/mm2) mitotic activity corresponding to the proliferation index values of Ki-67 <30%, 30%-50%, and >50%, respectively.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1026-A1026
Author(s):  
Lev M Berstein ◽  
Alexander O Ivantsov ◽  
Aglaya Iyevleva

Abstract Background and Aims: The last years were characterized by a shift from the former subdivision of endometrial cancer (EC) into two main types [1, 2] to modern molecular biological classifications of this disease [3-5]. The purpose of this investigation was an attempt to compare such prognostic indicators for EC as features of lymphocytic [6] and macrophage infiltration of tumor tissue with markers of its hormonal sensitivity (receptor phenotype) and the proliferation index Ki-67 [7], taking into account the molecular biological type of the disease. Materials and Methods: The study involved material from untreated patients with endometrial cancer (a total of 219 people). The average age of patients was close to 55-60 years. Using classification of Talhouk et al. [5] allowed to perform a search for POLE mutations, evaluate by IHC the expression of the oncoprotein p53 and MMR (mismatch-repair) proteins /MLH1, MSH2, MSH6 and PMS2/, and also identify the type of disease without a characteristic molecular profile (WCMP). The IHC method was also used to study the rate of estrogen (ER) and progesterone (PR) receptors, Ki-67 proliferative activity index, as well as the severity of macrophage-lymphocytic tissue infiltration of EC based on the analysis of the macrophage (CD68) and lymphocytic cells (cytotoxic CD8 and regulatory FoxP3) markers using reagents from Ventana and Dako. Statistical assessment of the relationships of the studied indicators was carried out by the Spearman rank correlation coefficient. Results: FoxP3 (in contrast to CD8 and CD68) positively and significantly correlates (ρ varies from 0.2895 to 0.3477) more often with ER, but not with PR. Ki-67 index in EC tissue positively and reliably correlates with FoxP3 both in the MMR-D and WCMP groups and in the combined cohort of EC patients. In the latter case, a similar relationship with Ki-67 extends to other studied markers of lymphocytic-macrophage infiltration, namely CD8 and CD68 (ρ 0,1746-0,3294). Only in the entire group of EC patients there is a positive rank correlation (0.4119!) between ER and PR expression. Conclusions: In patients with certain types of EC the connection between the estrogenic signal and PR induction is lost; it is especially noticeable in the MMR-D group, as exemplified by the negative correlation (-0.2951) of FoxP3 and PR expression. Taken together with existing data this indicates an important role of the endocrine component for differentiating separate groups of patients with EC, that may also be of practical importance. References: 1. Bokhman JV. Gynecol Oncol 1983; 15: 10-17. 2. Suarez AA et al. Gynecol Oncol 2017;144(2):243-249. 3. Murali R et al. Lancet Oncol 2014; 15: e268-278. 4.Berstein LM et al. Future Oncol. 2017 13(28):2593-2605. 5. Talhouk A. et al. Cancer. 2017;123(5):802-813. 6. Gargiulo P. et al. Cancer Treat Rev. 2016;48:61-8. 7. Kitson S. et al. Mod Pathol. 2017; 30(3): 459-468.


2021 ◽  
Vol 6 (5) ◽  
pp. 76-82
Author(s):  
V. V. Ilika ◽  
◽  
O. V. Garvasiuk ◽  
O. V. Ilika

The purpose of the study is to establish quantitative parameters of cell proliferation and apoptosis in the trophoblast of the chorionic villi in chorioamnionitis and basal deciduitis combined with iron-deficiency anemia in gravidas by means of immunohistochemical method. Materials and methods. 198 placentas were examined. The immunohistochemical procedure was performed using primary antibodies against Ki-67 and Bax antigen with imaging by a polymer system with diaminobenzidine dye. The number of Ki-67-positive nuclei of the chorionic villi trophoblast was counted, and for the Bax antigen, the optical density of the immunohistochemical staining was measured by means of microdensitometric method. Comparison of differences in mean trends was performed using the odd Student’s two-sided t-test (p≤0.05). Results and discussion. The number of Ki-67-positive trophoblast nuclei in acute chorioamnionitis with iron-deficiency anemia in gravidas was 56±3.8 ‰, and the relative units of optical density of immunohistochemical staining for protein Bax – 0.234±0.0012, in chronic – 59±3.6 ‰ and 0.2, respectively. The number of Ki-67-positive nuclei of the chorionic villi trophoblast was counted. Placentas with acute as well as chronic chorioamnionitis and basal deciduitis showed even higher averages (p <0.001). In acute basal deciduitis in anemia, the number of Ki-67-positive trophoblast nuclei was 56±3.2 ‰, the average optical density of immunohistochemical staining for protein Bax – 0.236±0.0016, in chronic – 57±3.7 and 0.249±0.0015, respectively. It should be noted that in chronic chorioamnionitis and basal deciduitis, these rates were higher than in acute. With the same regularity the average indicators of optical density of immunohistochemical staining on protein Bax in a trophoblast of chorionic villi at comorbid iron-deficiency anemia concerning an inflammation without anemia increase. We have shown that proliferative activity in iron-deficiency anemia varies with gestational age and placental prematurity, but iron-deficiency anemia in gravidas and chorionic tree maturation both individually and in combination lead to the intensification of these processes. We obtained a justification for the arithmetic mean thickness and volume of the placenta relative to observations of placenta with inflammation without anemia in this comorbid pathology. Conclusion. Iron-deficiency anemia in gravidas leads to the intensification of proliferative processes and Bax-dependent apoptosis in the trophoblast of the chorionic villi of the placenta relative to the placenta from physiological pregnancy. In acute as well as in chronic chorioamnionitis and basal deciduitis, the proliferative activity and apoptotic processes in the trophoblast of the chorionic villi of the placenta increase, while comorbid iron-deficiency anemia in gravidas intensifies only the processes of Bax-dependent apoptosis


2003 ◽  
Vol 40 (2) ◽  
pp. 203-206 ◽  
Author(s):  
V. Pace ◽  
S. Scarsella ◽  
E. Perentes

An anaplastic carcinoma was found in one of the two parathyroids of a 2-year-old male Wistar rat, which was sacrificed at the end of a carcinogenicity study. Morphologically, it was characterized by the presence of nodular areas of pleomorphic and dense cells with numerous atypical mitoses and large regions of smaller and dark monomorphic cells devoid of mitoses and forming small cystic spaces. Local invasion of the capsule and pronounced compression of the parenchyma of the thyroid gland were observed. Immunohistochemically, the tumor was markedly positive for the parathyroid hormone and negative for the thyroid transcription factor. The proliferative activity was assessed by immunostaining the endogenous cell proliferation associated-antigen Ki-67, and the proliferating cell nuclear antigen. The diagnosis of carcinoma of the parathyroid was made on the basis of microscopic and immunohistochemical findings.


2017 ◽  
Vol 34 (2) ◽  
pp. 92-99 ◽  
Author(s):  
Lisa A. Mestrinho ◽  
Hugo Pissarra ◽  
Sandra Carvalho ◽  
Maria C. Peleteiro ◽  
Jerzy Gawor ◽  
...  

Grade and labeling indices for immunohistochemical tumor proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) were evaluated in 36 cases of canine oral squamous cell carcinoma (OSCC) based upon intraoral location. Grade was significantly associated with location ( P = .035). Grade II tumors were most frequently diagnosed. Grade I tumors were identified in the gingiva and the buccal mucosa, and grade III tumors were seen in the gingiva and the tonsillar region. Animals with tumors arising from the tonsils and of the tongue tended to be older ( P = .007), and those in the former group were more likely to have metastatic disease at the time of diagnosis ( P = .001). Mean expression of PCNA and Ki-67 proliferation index (PI) for all tumors were 62.54% and 50.70%, respectively, and there was a statistical significant association between the 2 variables ( R = .70; P < .001). Proliferation index was not associated with any of the intraoral locations evaluated, but higher PCNA PI was significantly associated with grade ( P = .031). Ki-67 PI was significantly associated with lymph node metastasis at the time of diagnosis, especially for OSCC of gingival location ( P = .028). The results obtained in this study are preliminary but clinically relevant, since they provide information that can explain differences in biologic behavior among intraoral locations and contribute to more accurate tumor staging to support the choice for different treatment strategies available for OSCC.


2021 ◽  
Author(s):  
Bo Li ◽  
Shunli Jiang ◽  
Guangning Zhang ◽  
Junchen Zhang

Abstract Objectives: Glioma patients with brain tumor-related epilepsy (BTRE) have a complex profile due to the simultaneous presence of two pathologies: glioma and epilepsy. However, the underlying pathophysiology of BTRE remains poorly understood. The purpose of this study is to investigate the correlation between molecular neuropathology and glioma with BTRE.Methods: A retrospective cohort study of 186 glioma patients was evaluated at our hospital, with 64 presenting with BTRE. Chi-square test, spearman rank correlation and multivariate logistic analyses were used to identify clinicopathological factors associated with BTRE. Results: Of the 186 patients examined in this study, 64 (34.4 %) had BTRE. By analyzing the characteristics of these patients, the results showed that patient age (over 40 years; p=0.007), low WHO grade (grade I, II; p = 0.001), IDH-1 positive mutation (p=0.027), ATR-X low expression level (OR=0.44; 95% CI: 0.21, 0.92) and low Ki-67 proliferation index (OR=0.25; 95% CI: 0.10, 0.68) were associated with the occurrence of BTRE. BTRE did not differ by sex, tumor location, expression of olig-2 or CD34. The results of the matching study showed that low Ki-67 proliferation index and negative ATR-X expression level were independent factors for a higher incidence of preoperative seizures in glioma patients. Conclusion: The current study updates existing information on genetic markers in gliomas with BTRE and explores the correlation of a wide range of clinicopathological factors and glioma patients with BTRE. Our study suggests that three putative biomarkers for BTRE: positive IDH1 mutation, low Ki-67 proliferation index and negative ATR-X expression. These factors may provide insights for developing a more thorough understanding of the pathogenesis of epilepsy and effective treatment strategies aimed at seizure control.


2007 ◽  
Vol 131 (4) ◽  
pp. 530-537 ◽  
Author(s):  
John A. Ozolek ◽  
E. Leon Barnes ◽  
Jennifer L. Hunt

Abstract Context.—The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract. Objective.—To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles. Design.—Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34βE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin. Results.—Basal/myoepithelial cells in CS and REAH were positive for p63 and 34βE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34βE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2. Conclusions.—Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20−, and CDX-2−), contrasting with SNAC (CK7+, CK20+/−, CDX-2−/+).


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1261-1261
Author(s):  
Jean-Marie Bruey ◽  
Zeev Estrov ◽  
Hagop M. Kantarjian ◽  
Wanlong Ma ◽  
Chen-Hsiung Yeh ◽  
...  

Abstract Abstract 1261 Poster Board I-283 Ki-67 is a nuclear antigen that is expressed in all stages of the cell cycle except G0 and is widely used as a marker of cellular proliferation in human tumors. We recently demonstrated that levels of plasma circulating Ki-67 (cKi-67) are significantly higher in patients with newly diagnosed acute lymphoblastic leukemia (ALL) than in healthy control subjects, and that elevated levels of cKi-67 are associated with a shorter survival in ALL patients. Here we examined the associations of cKi-67 levels with laboratory and clinical variables in patients with chronic lymphocytic leukemia (CLL). The study included 194 patients with CLL and 96 healthy control subjects. The cKi-67 levels in plasma were determined using electro-chemiluminescence-based immunoassay using the Mesoscale Discovery platform. Since usually Ki-67 is used as an index of tumor cell proliferation, we took into account the lymphocyte count of the CLL patients in peripheral blood and normalized the levels of the cKi67 to the absolute number of lymphocytes in the peripheral blood establishing plasma cKI-67 index (cKi-67 level ng/1000 circulating lymphocytes/μL plasma). Median (range) levels of absolute cKi-67 were significantly higher in patients with CLL than in control subjects (914.65 [102.0-4975.12] ng/mL vs 353 [35.76-2830.65] ng/mL; P<0.0001). However, absolute levels did not correlate with clinical or other laboratory variables (white cell count, hemoglobin, platelets, beta-2 microglobulin, or Rai stage, performance status). In contrast, the cKI-67 index correlated significantly with bone marrow involvement (p<0.001), number of lymph node sites involved (p<0.001), and Rai stage (p=0.05), but not with IgVH mutation (P=0.62) or performance status (p=0.71) The cK-I67 index was significantly associated with survival when used as either as a continuous variable (P=0.002) or as a dichotomous variable (P=0.005). Multivariate Cox proportional hazards analysis incorporating cKi67 index with IgVH mutation status and B2M, demonstrated that only cKi-67 and B2M were independent predictors of survival. This data shows that there variability in proliferation between patients with CLL and those patients high relative proliferation (index) have more aggressive disease. Furthermore, plasma cKi-67 index and B2M levels are strong predictors of clinical behavior in CLL. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
pp. 34-48
Author(s):  
T. Yu. Skvortsova ◽  
Zh. I. Savintceva ◽  
D. V. Zakhs ◽  
A. F. Gurchin ◽  
A. I. Kholyavin ◽  
...  

The purpose of the study was to explore the correlation between 11С-methionine (Met) uptake measured by combined positron emission and computed tomography (PET/CT) in newly diagnosed cerebral gliomas and tumor proliferative activity as measured by Ki-67 labeling index (Ki-67 LI).The results of PET/CT with 11С-methionine (PET-Met) of 236 adult patients with pretreated glial brain tumors were included in retrospective analysis. The final diagnosis of glioma according to WHO classification of CNS tumors (2007) was based on both histology and immunohistochemistry using Ki-67 antibodies. On PET-Met tumor-to normal brain uptake ratio (TBR) was calculated by dividing maximum Met uptake in the tumor (hot spot 10 mm in diameter) to activity concentration in the contralateral cortex. The Spearmen rank correlation test was used to analyze the relationships between TBR and Ki-67 LI.PET-Met analysis showed that TBR increases with an increase in the aggressiveness of the glial tumor. The differences of TBR values between gliomas grade II vs III and grade III vs IV were significant (p < 0,001). Among grades II-III gliomas Met uptake was significantly higher in oligodendroglial and mixed gliomas than in astrocytomas (p < 0,001), but the differences did not depend on Ki-67 LI.Correlation analysis demonstrated significant correlation between Ki-67 LI and TBR values (r = 0,49, p < 0,05, Spearman rank test). With analyzing glioma subgroups TBR values correlated with Ki-67 LI in diffuse astrocytomas (r = 0,52, p < 0,05), oligodendrogliomas (r = 0,40, p < 0,05), oligoastrocytomas (r = 0,47, p < 0,05) and in high-grade gliomas (r = 0,45, p < 0,05) but not in low-grade gliomas. Comparison between TBR value and Ki-67 LI in each glioma showed a lack of coincidence in 22 % of cases (high Met uptake but low Ki-67 LI and vice versa). The main reasons for such discrepancies were tumor molecular biology or incorrect biopsy target.Met uptake in diffuse gliomas correlates with proliferative activity which justifies the use of PET-Met for glioma grading. In case of mismatch between two biomarkers one should rely on the indicator that implies a higher aggressiveness of the glioma.


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