Original article: Expression of p53 as predictor for the development of esophageal cancer in achalasia patients

Abstract

Patients with longstanding achalasia have an increased risk of developing esophageal cancer. Surveillance is hampered by chronic stasis. We investigated whether aberrant expressions of tumor suppressor gene p53 and proliferation marker ki67 are early predictors for progression to malignancy. In 399 achalasia patients, 4% died of esophageal cancer despite surveillance. We performed a cohort study, using surveillance biopsies from 18 patients (11 carcinoma, one high-grade dysplasia [HGD], and six low-grade dysplasia [LGD]) and 10 controls (achalasia patients without cancer or dysplasia development). One hundred sixty-four biopsies were re-evaluated and studied for p53 and ki67 expression using immunohistochemistry. Eighty-two percent of patients with cancer/HGD showed p53 overexpression in surveillance biopsies at a mean of 6 (1-11) years prior to cancer development. In 67% of patients with LGD and only in 10% of the controls p53 overexpression was present. The proportion of samples with p53 overexpression increased with increasing grades of dysplasia. We found no difference for ki67 overexpression. p53 overexpression may identify achalasia patients at increased risk of developing esophageal carcinoma. Further study is needed to determine if patients with p53 overexpression would benefit from intensive surveillance to detect esophageal neoplasia at a potential curable stage.

Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM) in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis

“…Leeuwenburgh evaluated the expressions of both p53 and Ki-67 in achalasia patients and reported that overexpression of p53 could be an early marker of neoplastic progression in achalasia [23]. In esophageal adenocarcinoma, Reid and Kerkhof reported that both p53 and Ki-67 were effective for early discrimination [24,25].…”

Esophageal squamous cell carcinoma co-existing with achalasia: report of two cases

“…Another pathological type of esophageal cancer, adenocarcinoma, arises from Barrett's epithelium, which is caused by gastroesophageal reflux secondary to myotomy or balloon dilation therapy. Pathological and biological examinations suggest that significant alterations including marked squamous hyperplasia and an increased frequency of p53 immunoreactivity may be related to the increased risk of squamous cell carcinoma [8,9]. One of our patients had two esophageal cancers, suggesting a precancerous achalasia status.…”

Esophageal Carcinoma

“…Leeuwenburgh et al 22 found that p53 overexpression increased with increasing grades of dysplasia and can be used to identify achalasia patients who are at increased risk of developing EC. It plays a very important role during the developing process of esophageal cancer (EC).…”

“…115 The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial randomized 503 patients with tumor located in stomach, GE junction, or lower esophagus into the surgery-alone group and perioperative chemotherapy group (three preoperative and three postoperative cycles of epirubicin, cisplatin, and 5-fluorouracil (5-FU)-ECF). infusion on days 1,8,15,22, and 29, with concurrent external beam radiation of 41.4 Gy/23 fractions. 119 According to the above evidence, NCCN guidelines recommend that preoperative chemotherapy be used only for adenocarcinoma located in the distal esophagus or GE junction, with ECF regimen as the first option.…”