In the present study, results showed that the MS patterns of EGC on me-nbi were significantly different in the gastric antrum and the corpus. Compared with the antral lesions, the grade of atypia in MS patterns was higher in corpus group. Based on the VS classification system, antral lesions were more likely to be ILL-1 type, while the corporal lesions were more inclined to be FNP type in those 2 groups of EGC.
In this study, the gastric pit pattern was evaluated according to the system proposed by Sakaki et al [19]. Although there are some limitations in this system, currently there is no other internationally recognized classification system for the assessment of gastric pits on upper digestive tract magnifying endoscopy. Therefore, this classification is still widely used in clinical practice [25]. According to the classification, the types of gastric pit pattern of EGC or precancerous gastric lesions mainly presented as IV, V1 or VI type [20]. In the present study, we found that the grade of atypia in MS patterns in the corpus type was more likely to be higher than in the antrum. In other words, the disordered or missing MS patterns in the corpus group were more obvious than the antrum group (Fig. 4-6).
That's an interesting finding. It is known that structural atypia and cellular atypia are key histopathological features for cancer diagnoses. ME-NBI can produce optical images reflecting structural atypia, which can achieve “optical biopsy” [8]. The structural atypia of gastric gland (or MS) of EGC may present as disordered or absent under ME-NBI. In that way, what’s the reason that the degree of MS atypia in the corpus group was significantly higher than that in the antrum group?
We speculate that this phenomenon could be explained by the structure of gastric wall mucosa, the occurrence of tumor epithelium, and the characteristics of tissue atypia. Histologically, the gastric pit comprises approximately 50% of antral mucosal thickness, but only 25% of corporal mucosal thickness. There is evidence showing that gastric stem cells usually reside in the base of gastric unit and gastric cancer stem cells (GCSCs) play an important role in the occurrence and development of gastric cancer [26]. Thus, we assume that the proliferation of GCSCs may cause gradual glandular morphological changes which arise from the bottom. The superficial glandular structure in the corpus is more susceptible to these changes because the crypts in the corporal mucosa are shallower. When the gastric mucosa becomes cancerous, corporal microsurface is prone to be disorganized, which can be easily observed on ME-NBI.
Previous researches have also proposed that the degree of differentiation of tumor tissue affects the appearance of the microsurface [9, 27]. Kanesaka et al [9] reported that the absence of MS patterns was the characteristic of U-EGCs because cancer cells in U-EGC usually failed to form glands and the original epithelial structure was often destroyed, while cancer cells in D-EGCs usually had epithelial glandular structures, which showed subtle structural atypia. Our study also suggested the structural atypia of MS patterns in U-EGCs was significantly different from that in D-EGCs, which was consistent with the pathological features of those 2 types of cancers.
However, the relationship between histological type factors and magnifying images may also be influenced by other common factors, such as depth of invasion [10], macroscopic morphology [13], and tumor location. Similarly, the relationship between tumor location and microstructure of EGC under me-nbi was also affected by other confounding factors, including depth of invasion and macroscopic morphology, in addition to histological type. In order to comprehensively analyzed whether those four factors were correlated with MS patterns, a common statistical method for multivariate analysis was employed to assess the whole cases in this study. The analysis confirmed that only tumor location and histologic type were independent predictors for MS patterns (Table 3).
As a result, in the EGCs, compared with the corpus, the atypia of MS pattern EGCs in the antrum were more subtle and thus their diagnosis might be more likely to be missed clinically. In daily endoscopic examination, there are usually multiple lesions coexisting in the gastric antrum, while EGC may only show slight changes in microstructure and microvascular patterns [28]. EGCs in the gastric antrum area are easily missed or difficult to distinguish from non-cancerous lesions due to the above reasons. Therefore, when equivocal lesions are found in the antrum, additional biopsies may be essential for inexperienced endoscopist.
Because the MV patterns and VS patterns were associated with the histologic type, invasion depth and macroscopic shape of lesions [9, 13], case control matching was employed to adjust these confounding factors before further analysis of tumor location. As a result, according to the MV classification used in this study, there was no significant difference in MV patterns between EGCs in the antrum and corpus. The microvessels in the superficial cancerous epithelium are deformed as a result of compression by the structurally atypical cancerous glands [29]. Thus, the secondary changes may not be different between the antrum type and the corpus type.
Yokoyama et al [13] reported that the distribution of VS patterns was significantly different between D-EGCs and U-EGCs. In this study, the classification categories between D-EGCs and U-EGCs were consistent with those reported by Yokoyama et al (Additional file 1: Table S1). As a result, the distribution of VS patterns was also significantly different between the corpus type and the antrum type of EGC. As we know, normal corporal mucosa appears as a regular honeycomb-like SECN pattern and regular oval crypt opening with circular MCE pattern [14]. Normal antral mucosa displays a regular coil-shaped SECN pattern and regular polygonal or curved MCE pattern [14]. FNP and ILL-1 are predominantly found in differentiated-type adenocarcinomas [13], in which there are still epithelial glandular structures with subtle structural atypia. Morphologically, FNP is similar to the normal corpus MS pattern and ILL-1 to the normal antral MS pattern. Correspondingly, in EGC lesions, FNP is mainly observed in the corpus type, while ILL-1 is more common in the antrum type.
However, the incidence of ILL-2 and CSP in the gastric antrum and gastric corpus is comparable. Based on previous work [13] and our findings (Additional file 1: Table S1), ILL-2 and CSP are mainly found in undifferentiated adenocarcinoma. We hypothesize that, since their glandular and epithelial structures are often destroyed in U-EGCs, the pattern of microstructure may not differ greatly between the antrum type and the corpus type. In clinical practice, these findings are helpful for the better understanding of the likelihood of these four VS categories in different sites and degrees of differentiation of EGCs.
There are also some limitations in this study. First, this was a retrospective study from a single center, and the sample size was relatively small. More multicenter, prospective studies are needed to confirm our findings. Second, no significant difference was observed between the MV patterns of EGCs in the antrum and corpus in the present study, according to the current MV classification. Whether this is related to the method used for classification of MV patterns is unclear.