Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

Gastrointestinal stromal tumors (GIST) constitue the largest category of primary non-epithelial neoplasms of the stomach and small bowel. They are characterized by a remarkable cellular variability and their malignant potential is sometimes difficult to predict. Very recent studies, using mitotic count and tumor size as the best determinants of biological behavior, divide GISTs into three groups: benign, borderline and malignant tumors. We report on a male patient who underwent a right hepatectomy for a large metastasis 11 years after the surgical treatment of an antral-pyloric gastric neoplasm, histologically defined as leiomyoblastoma and with clinical, morphological and immunohistochemical features of benignity (low mitotic count, tumor size < 5 cm, low cellular proliferation index). Histological and immunohistochemical analysis of the hepatic metastasis showed the cellular proliferation index (Ki-67) to be positive in 25% of neoplastic cells, as opposed to the primary gastric tumor in which Ki-67 was positive in only 5% of neoplastic cells. In conclusion, although modern immunohistochemical techniques are now available to obtain useful prognostic information, the malignant potential of GISTs is sometimes difficult to predict: neoplasms clinically and histologically defined as benign could metastasize a long time after oncologically correct surgical treatment. Therefore, benign GISTs also require consistent, long-term follow-up.

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Utility of preoperative computed tomography features in predicting the Ki-67 labeling index of gastric gastrointestinal stromal tumors

European Journal of Radiology ◽

10.1016/j.ejrad.2021.109840 ◽

2021 ◽

pp. 109840

Author(s):

Xiao-Shan Chen ◽

Ying-Chan Shan ◽

San-Yuan Dong ◽

Wen-Tao Wang ◽

Yu-Tao Yang ◽

...

Keyword(s):

Computed Tomography ◽

Gastrointestinal Stromal Tumors ◽

Labeling Index ◽

Ki 67 ◽

Stromal Tumors

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Immunohistochemical Expression of p16INK4A, Ki-67, and Mcm2 Proteins in Gastrointestinal Stromal Tumors: Prognostic Implications and Correlations with Risk Stratification of NIH Consensus Criteria

Annals of Surgical Oncology ◽

10.1245/s10434-006-9188-4 ◽

2006 ◽

Vol 13 (12) ◽

pp. 1633-1644 ◽

Cited By ~ 33

Author(s):

Hsuan-Ying Huang ◽

Wen-Wei Huang ◽

Ching-Nan Lin ◽

Hock-Liew Eng ◽

Shau-Hsuan Li ◽

...

Keyword(s):

Risk Stratification ◽

Gastrointestinal Stromal Tumors ◽

Immunohistochemical Expression ◽

Ki 67 ◽

Stromal Tumors ◽

Prognostic Implications ◽

Nih Consensus Criteria

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Virškinimo trakto stromos navikų diagnostika Valstybiniame patologijos centre 2003–2004 metais

Lietuvos chirurgija ◽

10.15388/lietchirur.2006.2.2271 ◽

2006 ◽

Vol 4 (2) ◽

pp. 0-0

Author(s):

Mindaugas Plečkaitis ◽

Ugnius Mickys ◽

Darius Dasevičius

Keyword(s):

High Risk ◽

Gastrointestinal Stromal Tumors ◽

Proliferative Activity ◽

Biological Behavior ◽

Cell Type ◽

Ki 67 ◽

Histological Features ◽

Stromal Tumors ◽

Cd 117 ◽

The Mean

Mindaugas Plečkaitis1, Ugnius Mickys2, Darius Dasevičius21 Vilniaus greitosios pagalbos universitetinė ligoninė,Šiltnamių g. 29 LT-04130, Vilnius2 Valstybinis patologijos centras,Baublio g. 5, LT-08406 VilniusEl. paštas: [email protected]; [email protected] Tikslas Išanalizuoti GIST atvejus, diagnozuotus Valstybiniame patologijos centre 2003–2004 m., apibendrinti histologinius šių navikų požymius, įvertinti histologinių požymių sąsajas su piktybinės biologinės elgsenos rizikos grupėmis. Medžiaga ir metodai Įvertinti pacientų amžių, pasiskirstymą pagal lytį, navikų lokalizaciją, daugybiškumą, metastazes, recidyvus. Papildomai įvertinti histologinius naviko požymius: histologinį piešinį (mišrus, šeivinis, epitelioidinis), organoidinių struktūrų formavimą, ritmines naviko ląstelių branduolių lygiavimosi (palisading) struktūras, ląstelių perinuklearinę vakuolizaciją, naviko miksoidinę stromą, koaguliacinę nekrozę, įsiskverbimą į savąjį gleivinės dangalą (lamina propria), dydį, mitozių kiekį, imunoprofilį. Remiantis navikų dydžiu ir mitozių kiekiu 50-yje didelio padidinimo regos laukų (pagal C.D.M. Fletcher), GIST suskirstyti į piktybinės biologinės elgsenos rizikos grupes. Rezultatai Ištirta 50 GIST atvejų. Ligonių amžiaus vidurkis 64,38 ± 14,26 metų, mediana – 68 metai. Moterų buvo 36, vyrų – 14. Nustatytos 7 (14%) GIST metastazės. Dauginių GIST diagnozuoti 4 atvejai (8%). Šių navikų recidyvų per tirtą laikotarpį nebuvo. Maždaug pusė pavienių navikų rasta skrandyje (45,7%), rečiau – plonojoje žarnoje (15,2%), rečiausiai – storojoje žarnoje (4,3%). Mišrių ir šeivinių GIST kiekis beveik nesiskyrė (atitinkamai 46,2% ir 43,6%), rečiau pasitaikė epitelioidinių navikų (10,3%). GIST dydis svyravo nuo 0,5 cm iki 25 cm (vidurkis 6,4 ± 5,3 cm; mediana 4,9 cm). Dauguma mūsų imunotipuotų GIST buvo teigiami CD 117 ir CD34 žymenims, o pusė navikų – teigiami a-lygiųjų raumenų aktinui. Didesnė dalis į rizikos grupes mūsų suskirstytų pavienių navikų (41,7%) buvo didelės piktybinės biologinės elgsenos rizikos. Koaguliacinė nekrozė buvo 86,7%, o naviko plitimo į savąjį gleivinės dangalą požymiai – 60% didelės piktybiškumo rizikos pavienių GIST. Ki-67 proliferacinis aktyvumas >10% naviko ląstelių populiacijos buvo būdingas didelės rizikos GIST, o Ki-67 proliferacinis aktyvumas <5% nekoreliavo su GIST piktybinės biologinės elgsenos rizikos grupėmis.. Išvada Tyrimo rezultatai parodė, kad naviko koaguliacinės nekrozės, plitimas į savąjį gleivinės dangalą, Ki-67 proliferacinis aktyvumas >10% naviko ląstelių populiacijos gali būti papildomi histologiniai kriterijai tikslesnei GIST prognozei nustatyti, nes yra būdingesni didelės rizikos GIST. Reikšminiai žodžiai: gastrointestininės stromos navikai, CD117, piktybinės biologinės elgsenos rizika Diagnostics of gastrointestinal stromal tumors in the National Centre of Pathology 2003–2004 Mindaugas Plečkaitis1, Ugnius Mickys2, Darius Dasevičius21 Vilnius University Emergency Hospital,Baublio str. 5, LT-08406 Vilnius, Lithuania2 National Center of Pathology,Akademijos str. 4, LT-08663 Vilnius, LithuaniaE-mails: [email protected], [email protected] Objective To review GIST cases diagnosed in 2003–2004 at the Lithuanian State Centre of Pathology, to evaluate the histological findings and to correlate histological features with the risk of malignant biological behavior. Materials and methods To evaluate the patiens’ age and sex distribution, localization, ]metastases, GIST relapses and multiple tumors. Additionally, to estimate the histological features: histological pattern (spindle, epithelioid or mixed cell type), nesting, palisading, perinuclear vacuolization of tumor cells, myxoid stroma, foci of coagulative necrosis, mucosal invasion, size, mitotic rate, immunophenotype and risk of malignant biological behavior (according to C.D.M. Fletcher) of GIST. Results Fifty GIST cases were analysed. The mean age of 36 females and 14 males was 64.38 ± 14.26 years, mediana 68 years. There were found 7 metastases (14%), 4 multiple GISTs (8%) and no one relapse case in our research. 45.7% of GISTs were localised in the stomatch, 15.2% in small intestine and 4.3% in large intestine. 46.2% of GISTs were of mixed type, 43.6% of spindle cell type and 10.3% of epithelioid type. The mean size of GISTs was 6.4 ± 5.3 cm, mediana 4.9 cm. Most of GISTs were positive to CD117 and to CD34, and one half of the tumors to a-actin. 41.7% of solitary GISTs showed a high risk of malignant biological behavior. Foci of coagulative necroses were found in 86.7% and mucosal invasion in 60% of solitary GISTs with a high risk of malignant biological behavior. Ki-67 proliferative activity >10% was characteristic of GISTs with a high risk of malignant biological behavior, whereas Ki-67 proliferative activity <5% did not correlate with the risk groups of malignant biological behavior. Conclusion The results of the research have shown that invasion of the mucosa, necrotic foci, Ki-67 proliferative activity more than 10% are characteristic of GISTs with a high risk of malignant biological behavior and should be used as additional predictors for the malignant potential of these tumors. Key words: gastrointestinal stromal tumors, CD 117, risk of malignant biological behavior

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Immunohistochemical features of gastrointestinal stromal tumors and their role for differential diagnosis and prognosis

EUREKA Health Sciences ◽

10.21303/2504-5679.2021.002183 ◽

2021 ◽

pp. 10-16

Author(s):

Yana Miroshnichenko

Keyword(s):

Differential Diagnosis ◽

Tumor Cells ◽

Gastrointestinal Stromal Tumors ◽

Spindle Cell ◽

Prognostic Markers ◽

Mitotic Rate ◽

Mesenchymal Tumors ◽

Ki 67 ◽

Stromal Tumors ◽

Strong Expression

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.

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