SDHB Staining in Sporadic GISTs: A Report from a Population-Based Italian Study (REGISTER Study).
Sabrina Rossi, Luisa Toffolatti, Daniela Gasparotto, Giovanna Gallina, Enrico Scaramel, Alessandra Marzotto, Luca Messerini, Italo Bearzi, Guido Mazzoleni, Carlo Capella, Giannatonio Arrigoni, Chiara Gnocchi, Paolo Casali, Roberta Maestro, Angelo Paolo Dei Tos. General Hospital, Treviso, Italy; C.R.O., Aviano, Italy; University School of Medicine, Firenze, Italy; University School of Medicine, Ancona, Italy; General Hospital, Bolzano, Italy; Ospedale di Circolo e Fondazione Macchi, Varese, Italy; Novartis Farma, Origgio, Italy; Istituto Nazionale Tumori, Milano, Italy; S. Raffaele, Milan, Italy
Background: It has been recently reported that GISTs of Carney triad and a subgroup of pediatric GISTs show loss of expression of succinate dehydrogenase B (SDHB), a subunit of mitochondrial complex II, whose inactivation is involved in tumorigenesis. In order to understand whether SDHB inactivation is also involved in the pathogenesis of sporadic GISTs, we investigated SDHB expression in the REGISTER series.
Design: Immunohistochemistry for SDHB (1:750, pH9 WB, clone 21A11 0, ABCAM) was performed on tissue microarray from 712 GISTs including 2 pediatric cases and 7 NF1 cases. Tumour cells were considered positive only if there was granular cytoplasmic staining, even weak or focal, and reliable only in presence of an internal positive control. Molecular analysis for KIT/PDGFRA was performed in a fraction of SDHB-negative cases. Clinico-pathological features of this group were compared to the whole series.
Results: Among 700 assessable cases, immunostain for SDHB was negative in 22 (3.1%). Clinico-pathological features of the latter group are shown in Table 1. Interestingly, in the SDHB negative subgroup, median age was slightly younger. One of the 2 pediatric GISTs was SDHB negative. SDHB-negative cases occurred more often in stomach, featured a higher mitotic activity and more frequently a mixed/epithelioid morphology. Unexpectedly, males were more than females. No difference in median tumor size was found. None of the NF1 cases belonged to the SDHB negative group. Despite the high proliferation activity, GIST progression occurred only in 5 out of 22 cases (median follow-up of 7.5 years). Six out of 9 (66%) SDHB negative GISTs were KIT/PDGFRA WT.
Conclusions: Loss of SDHB is observed in a small fraction of sporadic GISTs, mainly WT. Possible prognostic and predictive implications should be investigated.
|Register series||SDHB negative cases|
|Mitoses/50HPF||Median (range)||3.0 (0 - 262)||5.0 (0 - 146)|
|Mean (+/-SD)||12.1 (28.73)||20.5 (35.9)|