Usefulness of anti-phosphohistone H3 immunoreactivity to determine mitotic rate in gastrointestinal stromal tumors

2012 ◽  
Vol 5 (4) ◽  
pp. 91-97 ◽  
Author(s):  
Ahrong Kim ◽  
Dong Han Im ◽  
Kyungbin Kim ◽  
Jee Yeon Kim ◽  
Mee Young Sol ◽  
...  
2021 ◽  
pp. 10-16
Author(s):  
Yana Miroshnichenko

The aim. To clarify all most important immunohistochemical features of gastrointestinal stromal tumors with different histological patterns and analyze the role of expression of Ki-67, MMP-9, VEGF and p16ink4A as a predictive markers of tumor progression. Materials and methods. The study is based on analysis of 100 primary GISTs for description of their morphological features and 36 GISTs taken from this 100 for study of prognostic markers. Results. All spindle cell GISTs have shown diffuse expression of CD117 in tumor cells. The levels of CD117 expression varied from strong expression (3+) until mild expression (1+). Strong expression were seen in 75,8 % of spindle cell GISTs. Epithelioid GISTs demonstrated heterognous moderate or mild expression of CD117. All primary epithelioid GISTs from patients that had relapse of tumor in period from 1 till 3 years demonstrated focal mild expression of CD 117 in tumor cells. Expression of DOG-1 were seen in all 100 cases of GISTs, that were included in our study. The strong expression of DOG-1 (3+) were seen in all 45 GISTs that had low mitotic rate (≤5 mitoses per 50HPF) and not associated with their histological pattern. GISTs with high mitotic rate demonstrated heterogeneous expression of DOG-1 in tumors: moderate expression (2+) with patchy areas of strong expression (3+). Expression of CD56 was not found in spindle cell GISTs, but single tumor cells of epithelioid GISTs that had high mitotic rate demonstrated expression of this marker. The average expression of p16ink4A were higher in tumors that gave relapses compared with tumors without relapses (50,3 % versus 5,7 % respectively, U-test=16.5; p≤0,01).The average expression of MMP-9 also were significantly higher in GISTs that gave relapses: 63,2 % compared with 13,4 % in GISTs without relapse (U-test=16; p≤0 ,01).The strong VEGF expression was found in 66,7 % of GISTs that had relapses and only in 8,3 % of GISTs without relapses. 50 % of GISTs without relapses was negative for VEGF. Finally, the average expression of Ki-67 were 13,4 % in GISTs with relapses and 8,7 % in GISTs without them (U-test=16; p≤0,01). Conclusion. We highly recommend using DOG-1 for epithelioid GISTs. Additionally in epithelioid GISTs can be used CD56 that can give focal positive reaction in some tumour cells. The following minimal panel of markers for differential diagnosis of spindled GISTs from other mesenchymal tumors of gastrointestinal tract is proposed: CD117, DOG-1 and SMA, where the first too markers will demonstrated the moderate or strong diffuse expression and SMA can be occasionally positive in some tumor cells. p16ink4A, ki-67, VEGF and MMP-9 can be used as additional prognostic markers in GISTs.


2016 ◽  
Vol 82 (11) ◽  
pp. 1101-1104 ◽  
Author(s):  
Luke A. Kinsinger ◽  
James C. Garber ◽  
Oliver Whipple

With the increasing popularity of sleeve gastrectomy, many stomach specimens are being evaluated. Understanding the significance and treatment for unexpected pathology is important. This study examines the incidence of relevant histopathology of sleeve gastrectomy specimens. It evaluates previous data for each histopathology and provides recommendations for treatment. In this study, a retrospective review was performed for 241 patients who underwent sleeve gastrectomy from 2009 to 2014 at a single institution. Of the specimens, 122 had no significant histopathology, 91 had gastritis, 13 had lymphoid aggregates, 5 had hyperplasia, 3 had intestinal metaplasia, 3 had gastrointestinal stromal tumors (GISTs), and 3 had gastric polyps. Of the GISTs all had a low mitotic rate and the size of the tumor ranged from 1.5 to 4.5 cm. The findings of metaplasia may be a marker for increased risk of malignancy and may require additional surveillance. The findings of GIST may warrant interval imaging to survey for recurrence, though the likelihood of recurrence for the tumors in this study is less than 2 per cent based on previous studies.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 835-835
Author(s):  
Meera Garg ◽  
Kyle Joseph Hitscherich ◽  
Joseph J. Bennett

835 Background: Gastrointestinal Stromal Tumors (GISTs) are rare sarcomas with 5000 new cases each year. Despite their low incidence, surgeons should be familiar with this pathology since GISTs can be encountered incidentally during abdominal surgery. Methods: A retrospective series was conducted by querying pathology and operative reports from a community cancer center between 2005 and 2019 for all GIST diagnoses. Patients identified to have incidental GISTs discovered intra-operatively while undergoing surgery for another diagnosis were the focus of this study. Patient and tumor characteristics were evaluated. Results: A total of 195 patients had a diagnosis of a resected GIST during our study period. Of these 195, 48 patients were incidentally discovered to have a GIST excised during another index operation. The average age of these patients was 62 years old, 27 were female and 21 male. The primary location of these incidental GISTs in descending frequency was stomach (62.5%, n = 30), small bowel (31.3%, n = 15), colon (4.2%, n = 2) and esophagus (2.1%, n = 1). The average GIST size for the cohort was 1.7cm, with stomach, small bowel, colon and esophagus measured at 1.8cm, 1.7cm, 0.65cm and 0.30cm, respectively. Mitotic rate was < 5 mitosis/50 HPF in 96% of patients. Incidental GISTs were identified during the following surgery: colon (n = 14), bariatric (n = 13), non-bariatric gastric (n = 10), hernia (n = 4), pancreatic (n = 3), esophageal (n = 2) and other (n = 2). Most incidental GISTs were discovered during elective surgery (81.3%, n = 39) compared to emergency surgery (18.8%, n = 9), and for benign disease (n = 33) compared to malignant (n = 15). Conclusions: Approximately one quarter of all GISTs resected at our community cancer center in 15 years were discovered incidentally, and during a wide variety of abdominal surgeries for both benign and malignant disease. Almost all these GISTs were < 2cm, benign, and should be cured with the incidental resection. Abdominal surgeons should be aware of unexpectedly finding small GISTs and should not be apprehensive about resecting since they have indolent characteristics. Larger lesions should trigger expert surgical oncology consultation.


2014 ◽  
Vol 7 (3) ◽  
pp. 745-749 ◽  
Author(s):  
RALF KEMMERLING ◽  
DENIS WEYLAND ◽  
TOBIAS KIESSLICH ◽  
ROMANA ILLIG ◽  
ECKHARD KLIESER ◽  
...  

2021 ◽  
Author(s):  
Xiaohong Li ◽  
Yutao Zhang ◽  
Feng Li ◽  
Yun Tang ◽  
Hongyuan Zhou

Abstract BackgroundIt is well recognized that risk stratification of gastrointestinal stromal tumors (GISTs) is closely related to tumor size, mitotic index (MI), and primary location. Among these three parameters, tumor size and primary location are easily established, while MI is subjective and its repeatability is poor. It is thus necessary to identify a biomarker to represent the true MI. Expression status and biological or prognostic significance of mitotic marker phosphohistone H3 (PHH3) and cell proliferation marker Ki67 in GIST have not been clearly understood until now. MethodsAn immunohistochemistry experiment was performed to detect the expression status of PHH3 and Ki67 in 125 paraffin-embedded GIST samples. All of the patients were followed up until September 30, 2019. ResultsThe MI determined using stained hematoxylin and eosin (H&E) sections (MI-H&E) and immunohistochemically positive PHH3 index (PHH3-IHC) was compared among groups of different genders, ages, primary locations, and histological subtypes, showing that the difference was not statistically significant (P>0.05). MI-H&E and the immunohistochemically positive Ki67 index were positively correlated (r=0.273, P=0.001), but the correlation was lower than that with the PHH3-positive index (r=0.705, P=0.000). The PHH3-positive index was also positively correlated with the Ki67 index (r=0.224, P=0.006). MI-H&E were positively correlated with MI quantified using immunohistochemically stained PHH3 sections (MI-PHH3) (P<0.05). After using PHH3 to perform MI quantification, the risk stratification of five GIST cases was changed, where two cases were given a higher risk grade and three cases were given a lower risk grade. Follow-up data were obtained from 98 cases (98/125, 78.4%), including two cases of metastasis and one death. Both metastatic and death cases had high MI-H&E. One metastatic case and one death case had high PHH3-positive indexes, while the remaining metastatic case had a low PHH3-positive index. ConclusionImmunohistochemical PHH3 labeling is a potentially useful tool for risk stratification and prognostic analysis in GIST. Using immunohistochemical PHH3 labeling makes it more convenient for pathologists to determine the MI for GIST. MI quantification with immunohistochemical PHH3 sections can be used as an adjunct tool for risk stratification and prognostic analysis of GIST, but cannot completely replace MI quantification using stained H&E sections. The Ki67 index is positively correlated with MI-H&E, although the efficiency of tumor risk stratification is lower than that of PHH3.


2020 ◽  
Author(s):  
Xiaonan Yin ◽  
Yuan Yin ◽  
Lei Dai ◽  
Chaoyong Shen ◽  
Na Chen ◽  
...  

Abstract Background: Malignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. Methods: In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients’ prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Results: Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Conclusions: These results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20534-20534 ◽  
Author(s):  
Y. Shi ◽  
C. Du ◽  
H. Fu ◽  
G. Zhao ◽  
y. Zhou

20534 Objective: To investigate the prognostic factor of gastrointestinal stromal tumor. Methods: The clinicopathological data of 103 patients with gastrointestinal stromal tumors were analyzed restrospectively. Life table, kaplan-meier survival rate and cox regression model were used to evaluate the prognostic factors. Results: The 1 year ,3 years and 5 years total survival rate of these 103 gastrointestinal stromal tumors was 86.3%, 51.7%, 42.8%. Tumor size, mitotic rate, primary organ of tumor and radical surgical excision or not were analyzed respectively, the difference is statistical significance (P<0.05). No significiant difference between the group of sex, age, immunohistochemistry expression and multi-organ resection or not. Conclusion: Flechers’ classification is rational, scientific, simple and feasible. Radical surgical excision is the best therapy to the primary gastrointestinal stomal tumor. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10047-10047 ◽  
Author(s):  
G. Monges ◽  
J. Coindre ◽  
J. Scoazec ◽  
A. Bouvier ◽  
J. Blay ◽  
...  

10047 Background: GISTs are the most common mesenchymal tumors of the gastrointestinal tract but data on the annual incidence of this tumor is scarce due to previous lack of well-defined pathologic criteria. The aim of this study was to investigate the incidence of GISTs in France and describe the distribution according to age, sex, circumstances of discovery, localization and risk categories. Methods: This prospective epidemiologic study was performed among pathologists who were asked to declare all the cases of GIST over a one year period. All pathology centers (330 centers) in France were proposed to participate and asked to report exhaustively the cases diagnosed from 1 December 2004 to 30 November 2005. Results: 591 cases of GISTs were reported, 535 new cases and 56 cases of relapse. However, some large centers were not able to participate. So, the annual estimated incidence was 12 cases/million inhabitants in France. The main characteristics of the new cases of GIST were as follows: mean age 65 (± 13.2) (range: 16–93) years, 48.6% men and 51.4% women, circumstances of discovery: fortuitous 163 (30.5%), symptomatic 249 (46.5%), unknown 123 (23%). The primary tumor locations were: stomach 341 (63.7 %), small intestine 115 (21.5%), mesentery 35 (6.5%), colon/rectum 17 (3.2%), esophagus 4 (0.7%), unknown 23 (4.3%). 95.3% of GISTs were cKIT (CD117) + and 3.7 % were cKIT -. According to the Fletcher consensus criteria, based on tumor size and mitotic rate, among the 490 localized GISTs 14.7% were considered to be at very low prognostic risk, 25.5% at low-risk, 23.1 % at intermediate risk and 23.1 % at high-risk. For 13.6 % data were missing. Conclusions: This study is providing for the first time an estimation of the annual incidence of GISTs and a description of the characteristics of these tumors in France based on pathology registration. The true incidence may be slightly higher as some large centers were not able to reported their cases. These results are comparable to what has been reported in recent studies in other European countries. No significant financial relationships to disclose.


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