Majala Susanna, Vesterinen Tiina, Seppänen Hanna, Mustonen Harri, Sundström Jari, Schalin-Jäntti Camilla, Gullichsen Risto, Schildt Jukka, Kemppainen Jukka, Arola Johanna, Kauhanen Saila
Department of Surgery, Division of Digestive Surgery and Urology, Turku University Hospital, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland.
Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland.
Cancers (Basel). 2021 Dec 29;14(1):162. doi: 10.3390/cancers14010162.
The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs.
Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [Ga]Ga-DOTANOC and [F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [Ga]Ga-DOTANOC and [F]F-FDG PET/CT.
Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [Ga]Ga-DOTANOC finding (Spearman's rho 0.382, = 0.043). All [Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (-0.353, 95% CI -0.654-0.039, = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0-3.0) and 6.38 (SD 7.25, CI 2.25-8.75) for negative tumors.
SSTR2 was the only SSTR subtype to correlate with [Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
本研究旨在在前瞻性队列的神经内分泌性胰腺非功能性肿瘤（NF-PNENs）中，将SSTR1 - 5的免疫组化（IHC）组织水平与[镓]Ga-DOTANOC摄取所产生的受体密度进行关联分析。
本前瞻性研究纳入了21例患者，共有35个NF-PNEN病灶以及21个经组织学证实的淋巴结转移灶（LN+）。20例患者接受了手术，1例接受了内镜超声检查和粗针活检。所有患者均进行了[镓]Ga-DOTANOC和[氟]F-FDG的PET/CT检查。所有组织学样本均重新分类，并用单克隆SSTR1 - 5抗体、Ki-67进行IHC染色，并与[镓]Ga-DOTANOC和[氟]F-FDG PET/CT结果进行关联分析。
在74%、91%、80%、14%和77%的NF-PNENs中检测到SSTR1 - 5的表达。SSTR2 IHC结果与[镓]Ga-DOTANOC阳性/阴性结果存在一致性（Spearman等级相关系数0.382，P = 0.043）。所有摄取[镓]Ga-DOTANOC的肿瘤均表达SSTR2或SSTR3或SSTR5。在Ki-67增殖指数（PI）较低的肿瘤中，SSTR5的表达较高（-0.353，95%置信区间-0.654 - 0.039，P = 0.038）。SSTR5阳性肿瘤的平均Ki-67 PI为2.44（标准差2.56，置信区间1.0 - 3.0），阴性肿瘤为6.38（标准差7.25，置信区间2.25 - 8.75）。
SSTR2是唯一与[镓]Ga-DOTANOC PET/CT相关的SSTR亚型。我们的前瞻性研究证实SSTR2对SST PET/CT信号影响最大。
