American Association for Cancer Research
10780432ccr131239-sup-ccr-13-1239tab1.pdf (121.97 kB)

Supplementary Table 1 from Having Pancreatic Cancer with Tumoral Loss of ATM and Normal TP53 Protein Expression Is Associated with a Poorer Prognosis

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posted on 2023-03-31, 17:52 authored by Haeryoung Kim, Burcu Saka, Spencer Knight, Michael Borges, Erica Childs, Alison Klein, Christopher Wolfgang, Joseph Herman, Volkan N. Adsay, Ralph H. Hruban, Michael Goggins

PDF file - 123KB, PCR and sequencing primer sequences.



Purpose: To determine how often loss of ataxia-telangiectasia–mutated (ATM) protein expression occurs in primary pancreatic ductal adenocarcinomas and to determine its prognostic significance.Experimental Design: The expression of ATM and TP53 was determined by immunohistochemistry in 397 surgically resected pancreatic ductal adenocarcinomas (Hopkins; Johns Hopkins Medical Institutions, Baltimore, MD), a second set of 159 cases (Emory; Emory University Hospital, Atlanta, GA), and 21 cancers after neoadjuvant chemoradiotherapy. Expression was correlated with the clinicopathologic parameters, including survival.Results: Tumoral ATM loss was observed in one cancer known to have biallelic inactivation of ATM and 50 of the first 396 (12.8%) cases, significantly more often in patients with a family history of pancreatic cancer (12/49; 24.5%) than in those without (38/347; 11.0%; P = 0.019). In the Hopkins series, ATM loss was associated with a significantly decreased overall survival in patients whose cancers had normal TP53 expression (P = 0.019) and was a significant independent predictor of decreased overall survival (P = 0.014). Seventeen (10.7%) of 159 Emory cases had tumoral ATM loss and tumoral ATM loss/normal TP53 was associated with poorer overall survival (P = 0.1). Multivariate analysis of the combined Hopkins/Emory cases found that tumoral ATM loss/normal TP53 was an independent predictor of decreased overall survival [HR = 2.61; confidence interval (CI), 1.27–5.37; P = 0.009]. Of 21 cancers examined after neoadjuvant chemoradiotherapy, one had tumoral loss of ATM; it had no histologic evidence of tumor response.Conclusions: Tumoral loss of ATM protein was detected more often in patients with a family history of pancreatic cancer than in those without. Patients whose pancreatic cancers had loss of ATM but normal TP53 had worse overall survival after pancreatic resection. Clin Cancer Res; 20(7); 1865–72. ©2014 AACR.

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