• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.63-68
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• 2013

Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.

• Korean Journal of Radiology
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• v.22 no.3
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• pp.344-353
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• 2021

Objective: The mitotic count of gastrointestinal stromal tumors (GIST) is closely associated with the risk of planting and metastasis. The purpose of this study was to develop a predictive model for the mitotic index of local primary GIST, based on deep learning algorithm. Materials and Methods: Abdominal contrast-enhanced CT images of 148 pathologically confirmed GIST cases were retrospectively collected for the development of a deep learning classification algorithm. The areas of GIST masses on the CT images were retrospectively labelled by an experienced radiologist. The postoperative pathological mitotic count was considered as the gold standard (high mitotic count, > 5/50 high-power fields [HPFs]; low mitotic count, ≤ 5/50 HPFs). A binary classification model was trained on the basis of the VGG16 convolutional neural network, using the CT images with the training set (n = 108), validation set (n = 20), and the test set (n = 20). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at both, the image level and the patient level. The receiver operating characteristic curves were generated on the basis of the model prediction results and the area under curves (AUCs) were calculated. The risk categories of the tumors were predicted according to the Armed Forces Institute of Pathology criteria. Results: At the image level, the classification prediction results of the mitotic counts in the test cohort were as follows: sensitivity 85.7% (95% confidence interval [CI]: 0.834-0.877), specificity 67.5% (95% CI: 0.636-0.712), PPV 82.1% (95% CI: 0.797-0.843), NPV 73.0% (95% CI: 0.691-0.766), and AUC 0.771 (95% CI: 0.750-0.791). At the patient level, the classification prediction results in the test cohort were as follows: sensitivity 90.0% (95% CI: 0.541-0.995), specificity 70.0% (95% CI: 0.354-0.919), PPV 75.0% (95% CI: 0.428-0.933), NPV 87.5% (95% CI: 0.467-0.993), and AUC 0.800 (95% CI: 0.563-0.943). Conclusion: We developed and preliminarily verified the GIST mitotic count binary prediction model, based on the VGG convolutional neural network. The model displayed a good predictive performance.

• Biomedical Science Letters
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• v.17 no.3
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• pp.197-202
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• 2011

Mitosis count is one of the most helpful morphologic features for distinguishing pulmonary typical carcinoid (TC) from atypical carcinoid (AC). However, identifying areas of highest mitotic activity is tedious and time-consuming, and mitosis count may vary substantially among pathologists. Anti-phosphohistone H3 (PHH3) is an antibody that specifically detects histone H3 only when phosphorylated at serine 10 or serine 28, an event that is concurrent with mitotic chromatin condensation and not observed during apoptosis. In this study, immunohistochemical staining for PHH3 was performed to determine whether PHH3 was a reliable and objective mitosis-specific marker for pulmonary carcinoid tumors. Seventeen cases of surgically resected pulmonary carcinoid tumors (12 TCs and 5 ACs) were obtained and classified according to the 2004 World Health Organization classification. Mitotic counts determined by PHH3 correlated to ones determined by hematoxylin and eosin (H&E) staining; however, PHH3 mitotic counts (mean mitotic counts: 1 in TCs and 3.2 in ACs) were slightly higher than H&E mitotic counts (mean mitotic counts: 0.25 in TCs and 1.8 in ACs). The mitotic counts determined by experienced observer were more correlated to those determined by inexperienced observer with the PHH3-based method (R=0.968, P<0.001) rather than H&E staining (R=0.658, P<0.001). These results suggest that the PHH3 mitotic counting method was more sensitive and simple for detecting mitoses compared to traditional H&E staining. Therefore, PHH3 immunohistochemistry may contribute to more accurate and reproducible diagnosis of pulmonary carcinoid tumors and may be a valuable aid for administrating appropriate clinical treatment.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.259-264
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• 2001

Purpose : We investigated the temporal alterations of apoptosis and mitotic death following irradiation in the rat's small intestinal crypts. Materials and methods : Male Sprague-Dawley rats were irradiated 2 Gy by 6 MV linear accelerator and sacrified at 2, 4, 8, 24, 48 hours after irradiation. The mean numbers of the apoptotic cells and mitotic cells per their small intestinal crypts were measured in the unirradiated control and irradiated groups. To compare with H & E staining, ISEL (In Situ End Labelling) were peformed in the group having the highest apoptotic count. Results : The mean number of the apoptosis per crypt in the control group was 0.14 and those at 2, 4, 8, 24, 48 hours after irradiation were 1.43, 3.19, 1.15, 0.26, 0.17, respectively. So the apoptosis development was increased upto 4 hours and then normalized around 24 hours following irradiation. The mean number of the mitotic cells per crypt in the control group was 1.29 and those at 2, 4, 8, 24, 48 hours after irradiation were 0.56, 0.47, 0.23, 0.65, 1.19, respectively. The mitotic cell counts following irradiation was decreased to 8 hours and recovered to the normal level about 48 hours. So the increment of apoptotic cell count was occurred earlier and more remarkable than the decrement of mitotic cell count after irradiation. According to the staining time, false positivity was found in the ISEL staining. Conclusions : The cell death in the small intestinal crypt developed by acute radiation damage was usually decreased to the normal level within $24\~48\;hours$ after irradiation and the apoptosis was thought to be more important process than the mitotic death.

• Journal of Gastric Cancer
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• v.11 no.3
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• pp.173-179
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• 2011

Purpose: It is difficult to obtain biopsies from gastrointestinal stromal tumors (GISTs) prior to surgery because GISTs are submucoal tumors, despite being the most common nonepithelial neoplasms of the gastrointestinal tract. Unlike anatomic imaging techniques, PET-CT, which is a molecular imaging tool, can be a useful technique for assessing tumor activity and predicting the malignant potential of certain tumors. Thus, we aimed to evaluate the usefulness of PET-CT as a pre-operative prognostic factor for GISTs by analyzing the correlation between the existing post-operative prognostic factors and the maximum SUV uptake (SUVmax) of pre-operative 18F-fluoro-2-deoxyglucose (FDG) PET-CT. Materials and Methods: The study was conducted on 26 patients who were diagnosed with gastric GISTs and underwent surgery after being examined with pre-operative FDG PET-CT. An analysis of the correlation bewteen (i) NIH risk classification and the Ki-67 proliferation index, which are post-operative prognostic factors, and (ii) the SUVmax of PET-CT, which is a pre-operative prognostic factor, was performed. Results: There were significant correlations between (i) SUVmax and (ii) Ki-67 index, tumor size, mitotic count, and NIH risk group (r=0.854, 0.888, 0.791, and 0.756, respectively). The optimal cut-off value for SUVmax was 3.94 between "low-risk malignancy" and "high-risk malignancy" groups. The sensitivity and specificity of SUVmax for predicting the risk of malignancy were 85.7% and 94.7%, respectively. Conclusions: The SUVmax of PET-CT is associated with Ki-67 index, tumor size, mitotic count, and NIH classification. Therefore, it is believed that PET-CT is a relatively safe, non-invasive diagnostic tool for assessing malignant potential pre-operatively.

• Radiation Oncology Journal
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• v.33 no.1
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• pp.29-35
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• 2015

Purpose: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. Materials and Methods: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). Results: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. Conclusion: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.40-46
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• 2005

Purpose: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. Materials and Methods: 40 patients who underwent a complete resection of a GIST during the period $1996\~2003$ at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk. groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. Results: The mean age of the 40 patients was $61.3\pm11.1$years, and the male-to-female ratio was 1：1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, $Gleevec^{(R)}$). The treated patients have survived until now; however, two of non-treated patients died from disease progression. Conclusion: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.

• Journal of Digestive Cancer Research
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• v.10 no.1
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• pp.1-8
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• 2022

The incidence of gastric neuroendocrine tumors (NET) has been increased with the improvement of endoscopy accessibility. The World Health Organization classified NET of low (G1), intermediate (G2), high (G3) grade and neuroendocrine carcinoma with poor differentiation by mitotic count and Ki-67 labeling index. Gastric NET are divided into three subtypes based on the pathophysiology, and treatment is determined according to the subtype and prognostic factors of tumor. For diagnosis, endoscopy with biopsy, endoscopic ultrasonography, abdominal pelvis computed tomography, and serum gastrin level measure are required. In general, type 3, size > 2 cm, deep submucosal infiltration, high histological grade, lymphovascular invasion and metastasis are poor prognostic factors. Type 1 or 2 without these factors are treated by endoscopic resection, and other tumors needs surgery. Endoscopic resection of early type 3 or type 1 and 2 tumors with poor prognostic factors still remains a challenge.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.4
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• pp.380-387
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• 2023

Backgrounds/Aims: In 2019, the grading and staging system for neuroendocrine neoplasms (NENs) was significantly changed. In this study, we report the clinicopathological characteristics and surgical outcomes of patients with extrahepatic biliary NENs who underwent curative resection with or without adjuvant treatment. Methods: We retrospectively reviewed a database of 16 patients who developed NENs, neuroendocrine carcinoma (NEC), and mixed endocrine non-endocrine neoplasms (MiNENs) after curative resection. Among them, eight patients had ampulla of Vater (AoV) tumors, and eight patients had non-AoV tumors. Results: G1 and G2 were more frequently observed in the AoV group than in the non-AoV group (12.5% and 62.5%, respectively). In contrast, NEC and MiNEN were more common in the non-AoV group (50.0%). High Ki-67 index (> 20%) and perineural invasion (PNI) were more frequently observed in the non-AoV group. Advanced age (> 65 years), mitotic count > 20 per 2 mm², and Ki-67 index > 20% were strongly correlated with patient survival (p = 0.018, 0.009, and 0.044, respectively). Advanced age (> 65 years) and mitotic count > 20 per 2 mm² were significantly correlated with disease recurrence (p = 0.033 and 0.010, respectively). Conclusions: AoV and non-AoV tumors had significant differences in the histologic grade, Ki67, and PNI. Patients with non-AoV tumors had an increased risk for survival and recurrence than those in the AoV group. For extrahepatic biliary NENs, early detection of tumors, adequate surgery, and aggressive adjuvant treatment for high-risk patients are important to achieve long-term survival and prevent disease recurrence.

• Journal of Veterinary Clinics
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• v.31 no.1
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• pp.73-76
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• 2014

A 10-year-old, female spayed mixed-breed dog with a history of vomiting and anorexia was examined. Abnormal findings of comlete blood count and serum chemistry included polycythemia, thrombocytopenia, hyper-globulinemia and hypoalbuminemia. Abdominal radiographs revealed severe unilateral renomegaly, and ultrasonography showed a left-sided renal mass. During the operation, left kidney was resected. Cytologial and histopathological examinations revealed neoplastic lymphoid proliferation with high mitotic figures in renal mass. Immunohistochemistry revealed tumor cells were CD3-positive and CD79${\alpha}$-negative, consistent with T-cell lineage. The renal mass of this case was diagnosed as renal T cell lymphosarcoma.