Expression of DOG 1 and correlation with Ki-67 and tumor characteristics in GIST: case series analysis in a tertiary care center

Gastrointestinal stromal tumours (GISTs) are the most common non epithelial, mesenchymal tumours of the gastrointestinal tract and amount to 1 to 3% of all gastrointestinal tumours. Histologically, GISTs demonstrate considerable morphologic variation.The aim of the study was to evaluate the histo-morphological features of GIST and the expression of DOG1 and KI-67 in these tumours. Eleven cases of GISTs received during a five-year period at a tertiary care centre were analysed for their demographic parameters, morphology and risk stratification. Immunohistochemistry for DOG1 and Ki67 was performed for all the eleven cases.Inthis study there was a female preponderance with the mid -fifties being the median age of presentation. The stomach and small intestine were the common sites of involvement. The histologic type was predominantly spindle cell with a few cases of mixed tumours. DOG 1 was positive in all the tumours and Ki-67 index was markedly elevated in the epithelioid cell type and in the high-risk category of tumours.DOG 1 holds good as an important marker for clinically suspected GIST diagnosis and Ki-67 expression correlates with the risk stratification of the tumour and can be a good prognostic factor

Tumor del estroma gastrointestinal y trasplante renal / Gastrointestinal stromal tumor and renal transplant

El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Expression of DOG-1 and C-erbB-2 in papillary thyroid carcinoma and their clinical significance / 临床与实验病理学杂志

Purpose To investigate the expression and clinical significance of DOG-1 and C-erbB-2 in papillary thyroid carcinoma.Methods Immunohistochemical SP method was used to detect the expression of DOG-1 and C-erbB-2 protein in 48 cases of papillary thyroid carcinoma and 30 cases of benign thyroid lesions (15 cases of nodular goiter and 15 cases of Hashimoto's thyroiditis).Results The DOG-1 positive rate of thyroid papillary carcinoma (27.08％,13/48) was significantly higher than that of benign lesions (0,0/30),the difference was significant (P ＜ 0.05).The C-erbB-2 positive rate (39.58％,19/48) was significantly higher than that of benign lesions (3.33％,1/30),the difference was significant (P ＜ 0.05).Positive expression of DOG-1 as well as C-erbB-2 correlated with advanced TNM and presence of lymph node metastasis.The expression of DOG-1 and C-erbB-2 in patients with multifocal carcinomas combined with lymphatic metastasis showed a significant positive correlation(r =0.503,P =0.024).Conclusion The data suggest that DOG-1 and C-erbB-2 contribute to the pathogenesis and progress of thyroid papillary carcinoma.Our results introduce DOG-1 combined with C-erbB-2 as a promising biomarker for recurrence prediction and target therapy.

Malignant gastrointestinal stromal tumors (GISTs) of the duodenum – A rare occurrence: Case report.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Most of the cases are located in the stomach followed by the small intestine. They arise from the interstitial cells of cajal, which are located in the wall of the intestine. Malignant GISTs are rare type of tumors in GIT. Small intestine GIST is more likely to be malignant compared to stomach. Here we reported such a rare case of malignant GIST in a 54 years old female patient who came to the hospital with complaints of pain and mass in abdomen. Ultrasound revealed a mass originating from the duodenum. Provisional clinical diagnosis of duodenal carcinoma was considered preoperatively. Patient underwent complete surgical excision of the tumor. Histopathological examination confirmed the diagnosis of malignant GIST. As the recurrence rate for malignant GIST is high, patient was kept on follow up.

Oncocytic Lipoadenoma: A Rare Case of Parotid Gland Tumor and Review of the Literature

Oncocytic lipoadenoma is a rare tumor, with only 18 cases having been reported since the first in 1998. We encountered a case of oncocytic lipoadenoma presenting as a slowly growing parotid mass in a 71-year-old man. This tumor is characteristically comprised of a mixture of oncocytes and adipocytes. The present case is one of five reported cases of oncocytic lipoadenoma showing sebaceous differentiation. The results of immunohistochemical study with DOG1 antibody supported the origination of this tumor in the striated duct.

C-Kit-Negative Gastrointestinal Stromal Tumor in the Stomach

C-kit-negative gastrointestinal stromal tumors (GISTs) are uncommon, and there have been few reports about the diagnosis and treatment of c-kit-negative GISTs in the stomach. We report the case of a patient who was diagnosed with a huge and atypical GIST in the stomach. The GIST was completely resected and finally diagnosed as c-kit-negative GIST based on immunohistochemical staining of tumor cells, which were negative for CD117 and CD34 and positive for Discovered on GIST-1 (DOG1). C-kit-negative GISTs could be treated by complete resection and/or imatinib, which is the same treatment for c-kit-positive GISTs.

Multiple extragastrointestinal stromal tumors: a case report.

Gastro-Intestinal Stromal Tumor (GIST) is a non-epithelial, mesenchymal tumor. They most commonly originate from the stomach or small intestine, but in rare examples they involve the omentum in this article, we are reporting a case of multiple extragastrointestinal stromal tumour of the omentum, peritoneum and mesentery which was diagnosed cytologically and confirmed by histopathology and immunohistochemistry.

Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors

BACKGROUND/AIMS: The diagnosis of gastrointestinal stromal tumors (GIST) relies on the demonstration of KIT expression, but KIT expression is absent or reduced in approximately 15% of GIST. METHODS: Eighty-one GISTs were diagnosed between January 1998 and December 2007 at the Department of Pathology at both Chungnam National University Hospital and Eulji University Hospital, Daejeon. Medical history, patient follow-up, and radiographic data were collected if available in the medical records. To determine diagnostic and prognostic markers for GISTs focused on PDGFRA mutation and clinicopathologic features, we analyzed 81 GIST cases for KIT, PDGFRA, DOG1, and p16 expression and for mutation of PDGFRA genes. RESULTS: Among 81 GIST cases, 20 high risk cases (24.7%) were recurred or metastasized. Immunohistochemically, KIT was positive in 76 (93.8%), PDGFRA in 75 (92.7%), and DOG1 in 77 (95.1%). With a cutoff value of 50%, p16 expression was positive in 26 cases were positive (32.1%). A correlation between p16 expression or negative DOG1 expression and recurrence or metastasis was demonstrated (p<0.05). Four cases showed a missense mutation in exon 12 of PDGFRA gene, three of these were of epithelioid GISTs. Two cases showed a silent mutation in exon 18 of PDGFRA. CONCLUSIONS: These results indicate that the expression of DOG1 and PDGFRA is observed in a majority of GIST cases. Expression of p16 and negative DOG1 expression is predictive for development of recurrence and/or metastasis. Even though mutation of the PDGFRA gene is frequently seen in epithelioid GISTs, a clinicopathologic correlation was not demonstrated.

The expression of DOG1 in gastrointestinal stromal tumors / 中华普通外科杂志

Objective To evaluate DOG1 as an immunohistochemical marker for GIST.Methods From Jan 1987 to Sep 2008,210 consecutive cases including 137 GISTs as well as 73 non-GIST sarcoma were evaluated for clinicopathological characteristics and immunostained for DOG1 antibodies.Result Immunoreactivity for DOG1 was detected in 110 of 137 GIST cases (80.3%),3 out of 11 CD117negative GISTs were DOG1-positive.Only 1 of 73 non-GIST case was positive for DOG1.The expression of DOG1 in GIST is associated with the location of tumor,cell density,nuclear pleomorphism and Fletcher grading criteria.The postoperative 1-,3-,5-year overall survival for DOG1 negative and positive patients was 81.3%,74.5%,74.5% and 98.5%,85.9%,83.2%,respectively,P = 0.034.Conclusion DOG1 was a sensitive and specific marker for GIST in gastrointestinal mesenchymal tumors (GIMT).

Usefulness of DOG1 Expression in the Diagnosis of Gastrointestinal Stromal Tumors

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Expression of KIT protein (CD117) is an important diagnostic criterion of GIST. However, about 5% of GISTs are CD117 negative. Discovered on GIST 1 (DOG1) was introduced recently as a promising marker for GIST. We tested this new antibody in 105 GISTs tissue specimens, including 6 cases of metastatic GISTs, to determine the usefulness of DOG1 expression in the diagnosis of GISTs. METHODS: We performed immunohistochemical (IHC) staining for DOG1 and CD117 on tissue microarrays that included 70 gastric GISTs, 29 small intestinal GISTs, 6 metastatic GISTs, 14 gastric leiomyomas and 16 gastric schwannomas. RESULTS: DOG1 was positive in 98.1% (103/105) of GISTs and CD117 was positive in 97.1% (102/105) of GISTs. Only 1 case was negative for both markers. Two (66.7%) out of 3 GISTs tested CD117 negative were tested DOG1 positive. All leiomyomas and schwannomas were negative for both DOG1 and CD117. CONCLUSIONS: DOG1 was highly expressed in GIST including CD117 negative cases. Adding DOG1 testing to the IHC panel for diagnosing GIST will help to identify GIST patients who are CD117 negative but may otherwise benefit from targeted therapy.

Immunohisochemical differential diagnosis of mesenteric fibromatosis, solitary fibrous tumors and gastrointestinal stromal tumors / 中国现代普通外科进展

Objective: To study the immunohistochemical features and the differential diagnosis of mesenteric fibromatosis (MF), solitary fibrous tumors (SFT)and gastrointestinal stromal tumors (GIST). Methods: The expressions of CD117, CD34, ?-catenin, S-100, Desmin, Bcl-2 and Dog-1 of the three tumors were studied by immunohistochemistry method (S-P method). Results: By immunohistochemical staining detection, the expression of ?-catenin in six MF cases were positive, the positive expression rates of CD117 and Dog-1 in GIST cases were 85% and 92% respectively, and the positive expression rates of CD34 and Bcl-2 in SFT were 71% . Conclusion: MF, SFT and GIST can be identified by the combining applying of CD117,CD34 and ?-catenin through the immunohistochemistry method.