DIAGNOSTIC SIGNIFICANCE OF THE MARKER DOG–1 IN GASTROINTESTINAL STROMAL TUMORS

Dr. Haleema Beegum T. R; Dr. Sunitha Balakrishnan

Volume : VII, Issue : VI, June - 2017

DIAGNOSTIC SIGNIFICANCE OF THE MARKER DOG–1 IN GASTROINTESTINAL STROMAL TUMORS

Dr. Haleema Beegum T. R, Dr. Sunitha Balakrishnan

Abstract :

Background Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors that arise predominantly in the gastrointestinal tract (GIT). With the recent developments in the field of management of GISTs in the form of targeted therapies like Tyrosine Kinase Inhibitors (TKIs), the correct diagnosis of these tumors has a considerable clinical impact and great importance. In the vast majority of GISTs, high levels of CD117 expression are accompanied by a c–KIT gene mutation. A subset of GISTs has been found to have PDGFRA mutations rather than c–KIT mutations. Immunohistochemical marker CD117 will be positive in about 90–96% of GISTs. DOG–1 (“discovered on GIST”) is a calcium dependent, receptor activated chloride channel protein expressed in GIST and has been reported to be highly sensitive for GIST, for both KIT– and PDGFRA–mutated GISTs. The utility of DOG–1 is greatest in tumors lacking KIT and PDGFRA mutations. The present study evaluates the expression of the marker DOG–1 in gastrointestinal stromal tumors of GIT and correlates this with CD117 expression and various histomorphological features. Materials and methods The study was a cross sectional study done in Department of Pathology Government Medical College Thrissur, Kerala, India. Study period is from January 2010 to December 2014 (5 years). All the cases of Mesenchymal tumors of GIT during the same period received in the Department of pathology Govt Medical College Thrissur were included in the study. The various morphological parameters studied include gross dimensions of the tumour, predominant histological type, cellularity, presence or absence of tumour cell necrosis, mitotic Index and grade of the tumour along with Immunohistochemical staining for CD117 and DOG–1. Results There were a total of 33 cases. The age group ranged from 41–76 years. The mean age was 57 years. Males accounted for 54.5% of the cases with a male to female ratio of 1.2:1. Of the 33 cases, stomach was the commonest site of the lesion and accounted for 51.5 % of the cases followed by small intestine of which jejunum was the most common. Grossly, tumours with less than 10 cm and more than 10 cm size accounted for 60.6 % and 39.4 % respectively. In microscopy the predominant pattern of the tumors was spindle which constituted 57.6% followed by epithelioid pattern (27.3%). Mixed pattern was present in 15.2% of cases. 51.5 % of the cases showed a mitotic index of less than 5 per 50 HPF. 21.2 % of cases showed a high mitotic index of >10 per 50 HPF. Out of the 33 cases, CD 117 was positive in 23 cases which accounted for 69.6%. 10 cases were negative for CD 117 (30.3%). Out of the 33 cases 24 were positive for DOG–1(72.72%) and 9 (27.27%) were negative. The cases positive for CD117 or DOG–1 were considered as GIST. Those cases negative for DOG–1 and CD 117 (9 cases) were positive for other markers like SMA, Desmin and S–100. They were diagnosed as leiomyoma, leiomyosarcoma and schwannoma. Discussion The current study, evaluated DOG–1 antibody as a diagnostic marker for GISTs. The results demonstrated that DOG–1 is a specific and sensitive marker for GIST, as it stained all cases of GIST ie, 24 cases (100%) included in the study and didn‘t stain any of the other mesenchymal tumors tested. In the present study, a statistically significant concordance was found between the results of CD117 and DOG–1 immunoreactivity with perfect agreement between the two markers (K= 0.918). Twenty three (95.84%) cases of GISTs were positive for both markers. In our study DOG –1 was found to be more sensitive than CD117 (100 % and 95.8%). Negative predictive value of DOG –1 was higher than CD 117(100% and 90%). But the diagnostic accuracies of both DOG–1 and CD 117 were found to be equal (96.96%). Conclusion DOG–1 is a more sensitive immunohistochemical marker for GIST than c–KIT and we recommend using DOG–1 as the first choice antibody for the diagnosis of GIST. This study concluded that DOG–1 is a better IHC marker than c–KIT (CD117) in diagnosing GIST due to better sensitivity and negative predictive value. Since the diagnostic accuracy is the same for CD 117 and DOG–1, a combination of both must be considered in all the suspected cases of GISTs.