Jin Zhe, Tamura Gen, Honda Teiichiro, Motoyama Teiichi
Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.
Lab Invest. 2002 Dec;82(12):1637-45. doi: 10.1097/01.lab.0000041712.58604.cc.
According to the Padova international classification, 52 gastric noninvasive neoplasias (NIN) were classified as follows: 20 low-grade NIN (L-NIN); 9 high-grade NIN including suspicion for carcinoma without invasion (H-NIN); and 23 high-grade NIN including carcinoma without invasion (Ca-NIN). The molecular and cellular phenotypic profiles were investigated and compared. The APC gene was mutated in seven (35%) L-NIN, two (22%) H-NIN, and two (9%) Ca-NIN tumors; APC mutations were significantly more frequent in L-NIN compared with Ca-NIN tumors (p < 0.05). Mutations of the p53 gene were found in five (22%) Ca-NIN tumors but were not observed in L-NIN or H-NIN tumors (p < 0.05). Loss of heterozygosity involving at least one chromosomal locus was detected in 14 (61%) Ca-NIN tumors but was not detected in L-NIN or H-NIN tumors. High-frequency microsatellite instability (MSI-H) was detected in one (5%) L-NIN tumor and in six (26%) Ca-NIN tumors. The frequencies of loss of heterozygosity and MSI-H were significantly higher in Ca-NIN than in L-NIN or H-NIN tumors (p < 0.05). Nuclear accumulation of p53 protein was detected in no L-NIN tumors, 1 (11%) H-NIN tumor, and 10 (44%) Ca-NIN tumors (p < 0.01). All tumors with loss of hMLH1 expression exhibited MSI-H (p < 0.01). Cellular phenotypic analysis revealed that seven (35%) L-NIN tumors and one (4%) Ca-NIN tumor had complete-type intestinal metaplastic phenotype and that one (5%) L-NIN tumor and one (4%) Ca-NIN tumor had a gastric foveolar epithelial phenotype, whereas the remaining tumors exhibited an ordinary phenotype. Thus, the complete-type intestinal metaplastic phenotype was more characteristic of L-NIN tumors than of H-NIN or Ca-NIN tumors (p < 0.01). In summary, the Padova international classification correlated with both the molecular and cellular phenotypic profiles. In practice, p53 and hMLH1 immunohistochemistry discriminated Ca-NIN from L-NIN and H-NIN tumors.
根据帕多瓦国际分类法，52例胃非侵袭性肿瘤（NIN）分类如下：20例低级别NIN（L-NIN）；9例高级别NIN，包括可疑无侵袭性癌（H-NIN）；23例高级别NIN，包括无侵袭性癌（Ca-NIN）。对其分子和细胞表型特征进行了研究和比较。APC基因在7例（35%）L-NIN、2例（22%）H-NIN和2例（9%）Ca-NIN肿瘤中发生突变；与Ca-NIN肿瘤相比，L-NIN中APC突变明显更常见（p<0.05）。在5例（22%）Ca-NIN肿瘤中发现p53基因突变，但在L-NIN或H-NIN肿瘤中未观察到（p<0.05）。在14例（61%）Ca-NIN肿瘤中检测到至少一个染色体位点的杂合性缺失，但在L-NIN或H-NIN肿瘤中未检测到。在1例（5%）L-NIN肿瘤和6例（26%）Ca-NIN肿瘤中检测到高频微卫星不稳定性（MSI-H）。Ca-NIN中杂合性缺失和MSI-H的频率显著高于L-NIN或H-NIN肿瘤（p<0.05）。在L-NIN肿瘤中未检测到p53蛋白核积聚，在1例（11%）H-NIN肿瘤和10例（44%）Ca-NIN肿瘤中检测到（p<0.01）。所有hMLH1表达缺失的肿瘤均表现为MSI-H（p<0.01）。细胞表型分析显示，7例（35%）L-NIN肿瘤和1例（4%）Ca-NIN肿瘤具有完全型肠化生表型，1例（5%）L-NIN肿瘤和1例（4%）Ca-NIN肿瘤具有胃小凹上皮表型，而其余肿瘤表现为普通表型。因此，完全型肠化生表型在L-NIN肿瘤中比在H-NIN或Ca-NIN肿瘤中更具特征性（p<0.01）。总之，帕多瓦国际分类法与分子和细胞表型特征均相关。在实际应用中，p53和hMLH1免疫组化可区分Ca-NIN与L-NIN和H-NIN肿瘤。
