143P - NOTCH3 expression predicts poor survival in advanced esophageal squamous cell cancers

Background

Oesophageal cancer is the sixth leading cause of cancer-related mortality with more than 90% of oesophageal cancer being squamous cell carcinomas (ESCC) in Asian countries. Prognosis of ESCC remains extremely poor and identification of better prognostic factors is an unmet need.

Methods

We investigated the immune- histochemical expression of Notch1, Notch2, Notch 3, HES-1 (Hairy enhancer of Split -1) (a downstream transcription factor) and p21 among ESCC and non-tumour controls. Non-tumour controls consisted of diagnostic biopsies of GERD patients in which Barrett’s and erosive esophagitis had been ruled out. We also investigated the association of these markers with clinico-pathological features and survival. We included 46 patients of ESCC and 42 controls. IHC markers were performed according to the standard guidelines and analysed with a semi-quantitative H –score (The H score was calculated as: H score= D X I with values ranging from 1-15).

Results

The median age was 60 (37-78 years). M:F ratio was 30: 16. 65.2 % were smokers and 19.6 % were tobacco chewers. 38 cases were locally advanced (Stage III) and 8 were metastatic at baseline. Palliative intent therapy was offered to 24 % and definitive therapy to 76%. An ECOG -PS of 1,2 and 3 was observed in 26, 16 and 4 patients respectively. At a median follow up of 50.67 months, the median overall survival was10.47 mon (range= 8.23-15.1) mon. Using a cut-off score of 7.5 to define positivity, NOTCH 1,2,3 as well as p21 were found to be significantly over-expressed in ESCC as compared to normal controls, while there was no difference in Hes1 expression. Location, grade, baseline metastases, duration of symptoms showed no association with NOTCH 1,2 or 3 positivity. On univariate analysis, male sex, age >60 years, smokers, ECOG-PS>1, Notch 3 H score was found significant. On multivariate analysis, smokers (HR = 3.53, p = 0.013), ECOG-PS>1 (HR = 2.88, p = 0.006) and Notch3 H score (HR = 2.38, p = 0.047) emerged as independent adverse prognostic factors.

Conclusions

NOTCH 1,2 and 3 are highly expressed in ESCC as compared to controls. Notch3 H score is an independent predictor of survival in ESCC and merits evaluation in larger studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Raja Pramanik.

Funding

Intramural Research Fund, Research Section, All India Institute of Medical Sciences, New Delhi.

Disclosure

All authors have declared no conflicts of interest.