Aberrantly expressed GFRα-1/RET in patients with lacrimal adenoid cystic carcinoma is associated with high recurrence risk:a retrospective study of 51 LACC cases

Objective:Because of the poor prognosis of lacrimal adenoid cystic carcinoma(LACC),we aimed to investigate the effects of perineural invasion(PNI)and consequent aberrations in GDNF/GFRα-1/RET protein expression on LACC recurrence.Methods:Clinicopathological data for 51 histologically confirmed patients with LACC enrolled between 2001 and 2017 were retrospectively analyzed.Hematoxylin and eosin staining was applied to assess PNI.Tissue-based immunohistochemistry(IHC)detection of GDNF,GFRα-1,and RET proteins was performed on LACC formalin-fixed,paraffin-embedded specimens.We generated semi-quantitative data of the IHC results and compared them with the clinicopathological data for the 51 patients.Results:Of the 51 patients,19(37.3%)were PNI positive.Recurrence was more common for LACC with than without PNI(73.7%vs.37.5%,P=0.01).GDNF,GFRα-1,and RET proteins were expressed in 62.7%,62.7%,and 54.9%of the 51 patients with LACC,respectively.The expression of all 3 proteins was more common in patients with than without PNI.In agreement with previous findings,PNI-associated GFRα-1 and RET positivity,as detected by IHC,remained significantly associated with recurrence,whereas GDNF expression,as detected by IHC,was not correlated with LACC recurrence.Specifically,patients with concurrent GFRα-1 and RET expression may have a high risk of PNI(89.5%positivity rate)and recurrence(84.2%positivity rate).Conclusions:PNI may contribute to LACC recurrence.The concurrent expression of GFRα-1 and RET proteins,as detected by IHC,may potentially be associated with LACC PNI and recurrence.

Comparison of biological behavior of lacrimal gland adenoid cystic carcinoma with high-grade transformation cells

AIM:To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation(LACC-HGT)primar y cells cultured by high-grade transformation tissue and non-high-grade transformation(non-HGT)primary cells cultured by non-highgrade transformation tissue in proliferation,metastasis,drug susceptibility,and genes.METHODS:LACC-HGT primary cells were established by tissue block culture,and the 4^(th)to 10^(th)generation primary cells were selected as research objects.The cells were preliminarily identified by immunofluorescent staining.The differences between non-HGT and LACC-HGT primary cells in terms of proliferation,metastasis,and drug susceptibility were compared by cell counting kit-8(CCK-8)assay,wound healing,and drug sensitivity experiments.Differentially expressed genes were screened using mRNA array.Gene expression was analyzed using real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS:LACC-HGT primary cells were successfully cultured by tissue block culture.Immunofluorescence staining results showed that cytokeratin(CK)and CK7 expression levels were positive in LACC-HGT primary cells.CCK-8 results showed that the proliferation ability of LACCHGT cells was significantly higher than that of non-HGT cells.Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells.LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells.Compared with non-HGT cells,9566 differentially expressed genes were found in LACC-HGT primary cells,of which 5162 were upregulated and 4404 were down-regulated.The expression of N-acetylneuraminate pyruvate lyase(NPL),MARVEL domain containing 3(MARVELD3),syntabulin(SYBU),and allograft inflammatory factor 1(AIF1)was higher in LACCHGT cells than in non-HGT cells,whereas that of periostin(POSTN)was lower.CONCLUSION:LACC-HGT primary cells have faster proliferation,stronger migration ability,and poorer sensitivity to chemotherapy drugs than non-HGT primary cells.The expression of mRNAs in non-HGT and LACC-HGT primary cells are significantly different.These features are speculated to be the reasons why high-grade transformation tissues exhibit higher malignant degree and poorer prognosis than their counterparts.

Prognostic factors for lacrimal gland adenoid cystic carcinoma:a retrospective study in Chinese patients

AIM:To explore the prognostic factors for lacrimal gland adenoid cystic carcinoma(LGACC)in Chinese patients.METHODS:Clinical and histopathological data were reviewed in patients with pathologically confirmed LGACC.Local recurrence,metastasis,and disease-specific death were the main outcome measures.Univariate and multivariate analyses were performed by the Kaplan-Meier method and a Cox proportional hazard model.RESULTS:This retrospective cohort study included 45 patients with pathologically confirmed LGACC between January 2008 and June 2022.Tumor(T)classification(P=0.005),nodal metastasis(N)classification(P=0.018)and positive margin(P=0.008)were independent risk factors of recurrence;T(P=0.013)and N(P=0.003)classification and the basaloid tumor type(P=0.032)were independent risk factors for metastasis;T classification(P<0.001)was an independent factor of death of disease.In the further analysis,the durations from first surgery to radiotherapy is correlated with metastatic risk in LGACC patients with basaloid component(P=0.022).CONCLUSION:Histological subtype should be emphasized when evaluating prognosis and guiding treatment.Timely radiotherapy may reduce the risk of metastasis in patients with basaloid component.