Gastroscopic surveillance with targeted biopsies compared with random biopsies in CDH1 mutation carriers

Abstract

Background The International Gastric Cancer Linkage Consortium (IGCLC) consensus guideline advises prophylactic gastrectomy in early adulthood to prevent gastric cancer development in CDH1 germline mutation carriers; psychosocial reasons may postpone gastrectomy. We analyzed the yield of signet-ring cell carcinoma (SRCC) during surveillance gastroscopy in CDH1 mutation carriers.

Methods A retrospective analysis on surveillance gastroscopies in CDH1 mutation carriers was performed. The yield of SRCC in both targeted and random biopsies was studied. Endoscopic (biopsy) results were compared with the histopathologic outcomes in gastrectomy specimens.

Results 42 CDH1 mutation carriers (18 men; mean age 43, range 20–82 years) underwent 96 surveillance gastroscopies. SRCC lesions were identified on surveillance gastroscopy in 21 patients (50 %), by either targeted biopsies only (n = 11), random biopsies only (n = 3), or both random and targeted biopsies (n = 7). SRCC was detected in 41 /377 targeted biopsies (11 %), whereas random biopsies revealed SRCC in 14/1563 biopsies (0.9 %). At least one SRCC lesion was found in 26 of 30 gastrectomy specimens. In 18 of these 26 specimens (69 %), SRCC had been identified by endoscopic biopsies. Missed lesions were all small superficial SRCC foci, mainly in the body of the stomach.

Conclusion In our cohort of CDH1 mutation carriers, SRCC lesions were identified by an extensive endoscopic surveillance protocol in 69 % of SRCC-positive patients who underwent a gastric resection. The low number of SRCC detected through random sampling demands a critical reappraisal of random biopsy sampling in the IGCLC guideline.

• References

• 1 Hansford S, Kaurah P, Li-Chang H. et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol 2015; 1: 23-32
• 2 Pharoah PD, Guilford P, Caldas C. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology 2001; 121: 1348-1353
• 3 van der Post RS, Vogelaar IP, Carneiro F. et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. J Med Genet 2015; 52: 361-374
• 4 Correa P. Human gastric carcinogenesis: a multistep and multifactorial process- First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992; 52: 6735-6740
• 5 Carneiro F, Huntsman DG, Smyrk TC. et al. Model of early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for screening. J Pathol 2004; 203: 681-687
• 6 Humar B, Fukuzawa R, Blair V. et al. Destabilized adhesion in the gastric proliferative zone and c-Src kinase activation mark the development of early diffuse gastric cancer. Cancer Res 2007; 67: 2480-2489
• 7 Rocha JP, Gullo I, Wen X. et al. Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management. Histopathology 2018; 73: 878-886
• 8 Shaw D, Blair V, Framp A. et al. Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy?. Gut 2005; 54: 461-468
• 9 Mi EZ, Mi EZ, di Pietro M. et al. Comparative study of endoscopic surveillance in hereditary diffuse gastric cancer according to CDH1 mutation status. Gastrointest Endosc 2018; 87: 408-418
• 10 Fitzgerald RC, Hardwick R, Huntsman D. et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet 2010; 47: 436-444
• 11 Park CM, Reid PE, Walker DC. et al. A simple, practical ‘swiss roll’ method of preparing tissues for paraffin or methacrylate embedding. J Microsc 1987; 145: 115-120
• 12 Kluijt I, Siemerink EJ, Ausems MG. et al. CDH1-related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling. Int J Cancer 2011; 131: 367-376
• 13 Lee AF, Rees H, Owen DA. et al. Periodic acid-Schiff is superior to hematoxylin and eosin for screening prophylactic gastrectomies from CDH1 mutation carriers. Am J Surg Pathol 2010; 34: 1007-1013
• 14 van der Kaaij RT, van Kessel JP, van Dieren JM. et al. Outcomes after prophylactic gastrectomy for hereditary diffuse gastric cancer. Br J Surg 2018; 105: e176-e182
• 15 Hallowell N, Lawton J, Badger S. et al. The psychosocial impact of undergoing prophylactic total gastrectomy (PTG) to manage the risk of hereditary diffuse gastric cancer (HDGC). J Genet Couns 2017; 26: 752-762
• 16 Castro R, Pita I, Libanio D. et al. Random biopsies in patients harbouring CDH1 mutation: time to change protocol?. Endoscopy 2018; 50: S76
• 17 Gullo I, Devezas V, Baptista M. et al. Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease. Gastrointest Endosc 2018; 87: 1566-1575