Phagocytosis(cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas

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 least5%of the tumor.Tumor tissues from these 5 invasive gastric carcinomas were immunostained using an antimucin 1(MUC1)antibody(clone MA695)to detect the characteristic inside-out pattern and with D2-40antibody 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 d UTP-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(≥p T2)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 apoptoticneutrophils 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.

Changes in human epidermal growth factor receptor 2 status between primary breast/gastric carcinomas and synchronous metastatic lymph nodes: how can we explain them?

Aim:Previous studies demonstrated discordant expression of human epidermal growth-factor receptor 2(HER2)between primary cancer and their recurrence/metastasis.This study further evaluated HER2 status between primary gastric and breast invasive carcinomas and paired metastatic disease to lymph nodes.Methods:This study collected formalin-fi xed paraffi n-embedded representative tissue blocks from 62 gastric and 65 breast primary carcinomas as well as synchronous metastatic lymph nodes(male:female=39:88;age ranged between 44 and 95 years with mean age of 69.32 years)for immunohistochemical staining of HER2 expression(DAKO HercepTest^(TM)kit).If immunohistochemical HER2 score reached to 2+,HER2 amplifi cation was then assessed using fl uorescence in situ hybridization(PharmDx^(TM)kit DAKO).Results:The discordant HER2 pooled rate,regardless either negative or positive conversion,was 9.67%in primary gastric carcinoma and corresponding nodal metastasis,while the changes in HER2 expression were revealed in 4.61%of mammary and lymph node neoplastic samples.A high-level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was confi rmed in both types of cancer;the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity,mostly appreciable in gastric cancer.Conclusion:In any case,the shift from positive to negative HER2 expression suggests that trastuzumab could be the targeted treatment choice whereas the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes.