Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5548-5554
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5548
Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas
Valeria Barresi, Giovanni Branca, Antonio Ieni, Luciana Rigoli, Giovanni Tuccari, Rosario Alberto Caruso
Valeria Barresi, Giovanni Branca, Antonio Ieni, Giovanni Tuccari, Rosario Alberto Caruso, Department of Human Pathology, University of Messina, 98125 Messina, Italy
Luciana Rigoli, Department of Pediatrics, University of Messina, 98125 Messina, Italy
Author contributions: Barresi V and Branca G participated in the study conception, design and acquisition of data, contributed to the interpretation of data and drafted the manuscript; Ieni A, Rigoli L, Tuccari G and Caruso RA contributed to the acquisition and interpretation of data and helped draft the manuscript; all the authors read and approved the final manuscript.
Informed consent: All study participants in the present study provided written informed consent and the identities of all patients have been protected.
Conflict-of-interest: The authors declare that they have no competing interests.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luciana Rigoli, MD, Department of Pediatrics, University of Messina, 1 Via Consolare Valeria, 98125 Messina, Italy. lrigoli@unime.it
Telephone: +39-9-2212120 Fax: +39-9-2213788
Received: November 12, 2014
Peer-review started: November 15, 2014
First decision: December 2, 2014
Revised: December 30, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: May 14, 2015
Processing time: 186 Days and 23 Hours
Abstract

AIM: To identify those with a micropapillary pattern, ascertain relative frequency and document clinicopathological characteristics by reviewing gastric carcinomas.

METHODS: One hundred and fifty-one patients diagnosed with gastric cancer who underwent gastrectomy were retrospectively studied and the presence of a regional invasive micropapillary component was evaluated by light microscopy. All available hematoxylin-eosin (HE)-stained slides were histologically reviewed and 5 tumors were selected as putative micropapillary carcinoma when cancer cell clusters without a vascular core within empty lymphatic-like space comprised at least 5% of the tumor. Tumor tissues from these 5 invasive gastric carcinomas were immunostained using an anti-mucin 1 (MUC1) antibody (clone MA695) to detect the characteristic inside-out pattern and with D2-40 antibody to determine the presence of intratumoral lymph vessels. Detection of intraepithelial neutrophil apoptosis was evaluated in consecutive histological tissue sections by three independent methods, namely light microscopy with HE staining, the conventional terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemistry for activated caspase-3 (clone C92-605).

RESULTS: Among 151 gastric cancers resected for cure, 5 (3.3%) were adenocarcinomas with a micropapillary component. Four of the patients died of disease from 6 to 23 mo and one patient was alive with metastases at 9 mo. All patients had advanced-stage cancer (≥ pT2) and lymph node metastasis. Positive MUC1 immunostaining on the stroma-facing surface (inside-out pattern) of the carcinomatous cluster cells, together with negative immunostaining for D2-40 in the cells limiting lymphatic-like spaces, confirmed the true micropapillary pattern in these gastric neoplasms. In all five cases, several micropapillae were infiltrated by neutrophils. HE staining, TUNEL assay and immunostaining for caspase-3 demonstrated apoptotic neutrophils within cytoplasmic vacuoles of tumor cells. These data suggest phagocytosis (cannibalism) of apoptotic neutrophils by micropapillary tumor cells. Tumor cell cannibalism is usually found in aggressive tumors with anaplastic morphology. Our data extend these observations to gastric micropapillary carcinoma: a tumor histotype analogously characterized by aggressive behavior and poor prognosis. The results are of interest because they raise the intriguing possibility that neutrophil cannibalism by tumor cells may be one of the mechanisms favoring tumor growth in gastric micropapillary carcinomas.

CONCLUSION: This is the first study showing phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

Keywords: Gastric cancer; Micropapillary pattern; Mucin 1; Caspase-3; TUNEL assay

Core tip: Five rare cases of micropapillary carcinoma of the stomach are reported. Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells is demonstrated for the first time in micropapillary components of gastric carcinomas. These unique features might help us to better understand the aggressive behavior and poor prognosis of this rare entity.