Gastric Invasive Micropapillary Carcinoma with Intestinal Phenotypes Harboring a TP53 R175H Mutation

Abstract

We report a case of gastric invasive micropapillary carcinoma (IMPC) in an 86-year-old female patient. She was admitted to our hospital with a chief complaint of bloody emesis. Upper gastrointestinal endoscopy found a gastric adenocarcinoma at the antrum. The biopsy specimens showed moderately differentiated adenocarcinoma with invasive small tumor nests. Distal gastrectomy with systematic lymph node dissection demonstrated that the tumor had IMPC through a pathological examination. Despite the depth of tumor invasion (the submucosa), extensive lymph node metastases were observed. Anti-D2-40 immunostaining revealed numerous infiltrating tumor cell nests in the lymphatic vessels, which could explain subsequent multiple lymph node metastases. The adenocarcinoma showed intestinal phenotypes by several immunohistochemical studies. One of these antibodies (CD10) clearly demonstrated the inverted apical-basal (inside-out) pattern of IMPC, whereas it showed an ordinary pattern in intestinal metaplasia adjacent to the tumor. Furthermore, genetic analysis by direct sequencing revealed a point mutation in the exon 5 of TP53 in the tumor. The mutation presumably harbors a missense mutation from Arg to His at the codon 175 (R175H). R175H has been previously described as a ‘gain-of-function' mutation with a high invasive or metastatic potential in several types of cancers. In summary, this is one of the first reported cases of gastric IMPC with intestinal phenotypes harboring a TP53 R175H mutation in the literature.

Genomic alterations of oligodendrogliomas at distant recurrence

“…We observed that the same mutations were present in both the initial and recurrent samples (Figure 4). The TP53:p.R175H mutation is a functional acquired mutation closely related to the high invasiveness and metastatic potential of many cancers 20 . TP53:p.R273C is also a functional acquired mutation that promotes the proliferation, invasion, and drug resistance of tumor cells 21 .…”

“…The TP53:p.R175H mutation is a functional acquired mutation closely related to the high invasiveness and metastatic potential of many cancers. 20 TP53:p.R273C is also a functional acquired mutation that promotes the proliferation, invasion, and drug resistance of tumor cells. 21 The 1p/19q co‐deletion is positively associated with IDH mutations, while it is mutually exclusive with ATRX loss and TP53 mutation, which are the hallmarks of diffuse astrocytoma.…”

Progression inference for somatic mutations in cancer

“…PBAM results for stomach adenocarcinoma can be found in Figure 16 . We identified that mutations in ARID1A, LRP1B, and TP53 [172] , [173] formed three major parent nodes. Mutation in ARID1A appears to be causal to chains of alterations within the same gene.…”