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In Reply:

Institut Universitaire de Pathologie, Lausanne, Switzerland

Jean-Michel Coindre

Département de Pathologie, Institut Bergonié, Bordeaux, France

We thank Dr Marc Ladanyi for his interest in our work. In 2002, Ladanyi et al¹ suggested that fusion type might be of prognostic value in patients with synovial sarcoma. However, we were unable to confirm their results in a subsequent study with a similar design.² In this situation, the first question to be addressed is, "Why have apparently similar studies generated different results?" There are many possible reasons for that, including variations in patient (eg, age and sex) and tumor characteristics (eg, tumor site, size, grade, histology, and so on). Since prognostic studies are primarily based on patient outcome, it is obvious that treatment modalities may also have a significant impact. As pointed out by Dr Ladanyi (and we entirely agree with him on that point), it is evident that treatment schemes cannot be compared from one multi-institutional study to another, and furthermore, even from one patient to another within the same cohort (treatment schemes may vary not only according to patient and tumor characteristics, but also according to the level of equipment of the institutions and period of treatment). Despite these inevitable biases inherent in retrospective analyses, one might still expect concordant results. Indeed, the results from the study by Ladanyi et al are not strikingly different from ours. We both observed a significant association between patient sex and fusion type, and both confirmed that biphasic synovial sarcomas were rarely associated with the SYT-SSX2 fusion. However, Ladanyi et al found that the SYT-SSX1 fusion was associated with a reduced overall survival rate in univariate and multivariate analyses but the level of significance was not high (P = .08 and P = .04 in univariate and multivariate analyses, respectively, for patients with localized disease at presentation).¹ In addition, in their multivariate analyses, they failed to include recognized prognostic factors such as mitotic activity, tumor necrosis, and/or poorly-differentiated morphology, omissions that are, in our opinion, sufficient to explain their observation that fusion type was prognostically significant.

Along with Ladanyi et al,¹ we observed a tendency for SYT-SSX1 tumors to localize in extremities. In our series, axial tumors behaved significantly more aggressively than free-limb tumors, and as rightly stressed by Dr Ladayni, patients with axial tumors experienced a higher level of tumor relapses as compared with those with free-limb tumors. Since SYT-SSX2 and SYT-SSX1 fusions predominated in axial and free-limb tumors, respectively, it is possible that the difference in terms of prognosis was not related to fusion type but merely to tumor location and quality of surgical excision. Thus, we specifically examined outcomes in the subpopulations of patients with free-limb and axial tumors. For patients with free-limb tumors localized at diagnosis (n = 99), there was no significant difference between SSX1 (n = 75) and SSX2 (n = 24) fusions in terms of disease-specific survival (DSS; P = .95) and metastasis-free survival (MFS; P = .96). For patients with axial tumors, SSX2 fusions (n = 18) tended to be associated with more aggressive behavior than SSX1-bearing lesions (n = 24; P = .03 for DSS; P = .59 for MFS). Thus, the better prognosis of SSX1 tumors cannot totally be ascribed to their predominant free-limb localization, whereas the inverse holds true for SSX2 lesions.

In the Guillou et al study,² SYT-SSX2–bearing tumors tended to be metastatic at presentation more frequently than SYT-SSX1 tumors (P = .15), whereas the opposite was observed in the Ladanyi et al study.¹ In the former study, this unexpected difference cannot be explained by a bias for axial tumors as compared with free-limb tumors in the subset of patients with metastatic disease at presentation, as each group (axial v free-limb) had an equal number of patients (n = 12).

SSX1-bearing tumors were more frequent in our series, especially within the subset of patients with localized disease at presentation (99 SSX1 v 42 SSX2 patients). As underlined by Dr Ladanyi, we cannot exclude that this may have influenced our results. However, despite the fact that there were more patients with SSX1 tumors in our series (who were reported to be of poorer prognosis by some studies^1,3), their outcome, in terms of DSS and MFS, was not significantly different from that of the patients with SSX2 tumors. This suggests that the poor prognosis ascribed to SSX1 tumors is probably not as important (in terms of prognostic weight) as previously thought.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Ladanyi M, Antonescu CR, Leung DH, et al: Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: A multi-institutional retrospective study of 243 patients. Cancer Res 62 : 135 -140, 2002[Abstract/Free Full Text]

2. Guillou L, Benhattar J, Bonichon F, et al: Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: A multicenter, retrospective analysis. J Clin Oncol 22 : 4040 -4050, 2004[Abstract/Free Full Text]

3. Nilsson G, Skytting B, Xie Y, et al: The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res 59 : 3180 -3184, 1999[Abstract/Free Full Text]

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Related Correspondence

• Correlates of SYT-SSX Fusion Type in Synovial Sarcoma: Getting More Complex But Also More Interesting?
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