Neri Giuseppe, Arpa Giovanni, Guerini Camilla, Grillo Federica, Lenti Marco Vincenzo, Giuffrida Paolo, Furlan Daniela, Sessa Fausto, Quaquarini Erica, Viglio Alessandra, Ubezio Cristina, Pasini Alessandra, Ferrero Stefano, Sampietro Gianluca, Ardizzone Sandro, Latella Giovanni, Mescoli Claudia, Rugge Massimo, Zingone Fabiana, Barresi Valeria, Ciccocioppo Rachele, Pedrazzoli Paolo, Corazza Gino Roberto, Luinetti Ombretta, Solcia Enrico, Paulli Marco, Di Sabatino Antonio, Vanoli Alessandro
Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy.
Pathology Unit, Department of Surgical and Diagnostic Sciences, University of Genoa and Ospedale Policlinico San Martino University Hospital, 16132 Genoa, Liguria, Italy.
Cancers (Basel). 2020 Nov 19;12(11):3441. doi: 10.3390/cancers12113441.
Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn's disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7-/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7-/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7-/CK20- or CK7-/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20- or CK7+/CK20+ cancers ( = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7-/CK20- cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.
富含AT序列的特殊结合蛋白2（SATB2）是一种转录因子，由结肠隐窝上皮以及下消化道（GI）上皮肿瘤表达，小肠腺癌（SBA）也可表达，不过表达率较低。然而，到目前为止，仅对少量SBA病例系列进行了SATB2表达情况的研究，这些系列通常包含数量非常有限的克罗恩病相关SBA（CrD-SBA）和乳糜泻相关SBA（CD-SBA）。我们评估了100例SBA中SATB2及其他GI表型标志物（细胞角蛋白（CK）7和CK20、尾型同源盒蛋白2（CDX2）和α-甲基酰基辅酶A消旋酶（AMACR））以及错配修复（MMR）蛋白的表达情况，其中包括34例CrD-SBA、28例CD-SBA和38例散发性病例（Spo-SBA）。研究了其与其他临床病理特征（包括患者预后）之间的相互关联及相关性。共鉴定出20例（20%）SATB2阳性SBA（4例CrD-SBA、7例CD-SBA和9例Spo-SBA）。与CD-SBA（25%）和Spo-SBA（24%）相比，CrD-SBA中SATB2阳性的患病率较低（12%）。有趣的是，6例SBA（2例CD-SBA和4例Spo-SBA）表现出完全的结直肠癌（CRC）样免疫表型（CK7-/CK20+/CDX2+/AMACR+/SATB2+）；其中没有CrD-SBA。未观察到SATB2表达与MMR状态之间存在关联。虽然与SATB2阴性患者相比，SATB2阳性SBA患者的预后似乎更佳，但差异未达到统计学意义。根据CK7/CK20表达模式对癌症进行分层时，我们发现CK7-/CK20-的SBA中MMR缺陷病例富集（71%），与CK7+/CK20-或CK7+/CK20+癌症患者相比，CK7-/CK20-或CK7-/CK20+的SBA患者的生存率显著更高（P = = 0.002）。总之，我们鉴定出一小部分（6%）具有完全CRC样免疫表型的SBA，这在试图确定原发部位不明肿瘤的起源部位时可能是一个潜在的诊断陷阱。与结直肠癌的数据相反，SATB2表达与SBA中的MMR状态无关。CK模式影响患者生存，因为CK7-/CK20-癌症显示出更好的预后，这种表现可能是由于该亚组中MMR缺陷SBA的比例较高。
