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【Objective】 To investigate the expressions of H3.3G34W, p63 and SATB2 in giant cell tumor of bone (GCTB) and the effect and value of their combined application in the diagnosis of GCTB. 【Methods】 We collected the samples and medical records of 54 cases of GCTB and 83 cases of non-giant cell tumor of bone (14 cases of aneurysmal bone cyst, 16 cases of chondroblastoma and 53 cases of non-ossifying fibroma) diagnosed between 2020 and 2022 in the Department of Pathology of Honghui Hospital Affiliated to Xi’an Jiaotong University. The expressions of H3.3G34W, p63 and SATB2 were detected by EliVision immunohistochemical method. χ2 test was used to determine whether there are significant differences in the positive rates of H3.3G34W, p63 and SATB2 among all the groups. The combined diagnostic model including H3.3G34W, p63 and SATB2 was established by Logistic regression analysis, and the diagnostic value of the model was evaluated by ROC curve analysis. 【Results】 The positive rates of H3.3G34W, p63 and SATB2 in GCTB group were 81.5%, 90.7% and 92.6%, respectively; the positive rates in NGCTB group were 2.4%, 28.9% and 62.7%. Compared with NGCTB group, the age of GCTB group was significantly older [(41.222±14.849) vs. (16.566±9.439) , P<0.001] , and the prevalence was higher in women than in men (51.9% vs. 48.1%, P<0.001). In addition, compared with the NGCTB group, the positive rates of H3.3G34W (81.5% vs. 2.4%, P<0.001), p63 (90.7% vs. 28.9%, P<0.001) and SATB2 (92.6% vs. 62.7%, P<0.001) were significantly higher in the GCTB group. Univariate regression analysis built a univariate prediction model and ROC curve analysis showed that age (AUC=92.9%, P<0.001), sex (AUC=64.5%, P=0.004), H3.3G34W positive rate (AUC=89.5%, P<0.001), p63 positive rate (AUC=80.9%, P<0.001) and SATB2 positive rate (AUC=65.0%, P=0.003) were independent predictors of diagnosis of giant cell tumor of bone. Multivariate regression analysis (Logistic) constructed a hybrid prediction model. ROC curve analysis suggested that the hybrid model showed better prediction value than the single factor model (AUC=98.4%, P<0.001). 【Conclusion】 H3.3G34W, p63 and SATB2 are effective molecular markers for the diagnosis of GCTB, and their combined application can improve the prediction efficiency of the diagnosis of GCTB.
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Context: The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations. Objectives: To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions. Design: Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive. Results: Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%. Conclusion: The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB.
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Objective@#To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB.@*Methods@#Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019.@*Results@#Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%.@*Conclusions@#H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation.
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To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Immunohistochemical (IHC) EnVision method was used to detect the expression of H3.3 G34W mutant-specific antibody and p63 in 83 GCTBs, 18 aneurysmal bone cysts, 23 chondroblastomas and 28 osteosarcomas diagnosed at Nanjing Jinling Hospital from June 2001 to April 2019. Among the 83 cases of GCTB, 69 cases (69/83, 83.1%) expressed H3.3 G34W. H3.3 G34W expression was found exclusively in the mononuclear cell population with strong and diffuse nuclear staining. H3.3 G34W was expressed in 55 of 57 (96.5%) cases of GCTB in long bones, but only 14 of 26 (53.8%) cases of non-long bone GCTB. All recurrent (9/9)/metastatic GCTB (2/2), post-denosumab GCTB (3/3), primary malignant GCTB (3/3) and secondary malignant GCTB (5/5) also expressed H3.3 G34W. H3.3 G34W was negative in all aneurysmal bone cysts and chondroblastomas. H3.3 G34W was positive in 3 of 28(10.7%) cases of osteosarcomas, and giant cell-rich osteosarcoma(GCRO) was the only histological subtype of osteosarcoma that expressed H3.3 G34W. p63 was expressed in 71.1%(59/83) of GCTB, while the positive rates of p63 in aneurysmal bone cysts,chondroblastomas and osteosarcomas were 3/18, 43.5% (10/23) and 21.4% (6/28) respectively. The sensitivity and specificity of H3.3 G34W mutant-specific antibody in the diagnosis of GCTB were 83.1% and 95.7%. H3.3 G34W mutant-specific antibody is a highly sensitive and specific marker for GCTB and helpful for the diagnosis of GCTB and its variants. The limitation of this antibody is that as a mall number of GCTB harbor G34 mutation other than G34W, and thus that cannot be detected. The incidental expression of H3.3 G34W mutant protein in osteosarcoma could be a potential diagnostic dilemma, and the results of H3.3 G34W IHC staining needs careful interpretation.