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Sarcoma

P64: MasSpec Pen Technology for Molecular Identification of MPNST Surgical Margin Assessment

Introduction: NF1-associated malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with propensity for local recurrence and metastatic spread. Surgical resection is the only curative approach for these chemo- and radio-resistant tumors. Surgeons rely on the pathological evaluation of margins to assess the adequacy of resection, yet current methods for intraoperative tissue evaluation can be time intensive. More efficient technologies are critical for accurate MPNST margin assessment intraoperatively.

Methods: Ten MPNSTs and 13 neurofibromas (NF) were identified. Normal fat, nerve, skeletal, and smooth muscle tissues were used as controls. We obtained mass spectra for all samples using the MasSpec Pen system integrated to an Orbitrap mass spectrometer. Data obtained from histologically validated tissues were evaluated blindly by board-certified sarcoma pathologists. Molecular models for tissue classification were built. Statistical models were generated using machine learning and assessed using validation and test sets.

Results: Mass spectra obtained from the MPNST and neurofibroma samples demonstrated molecular profiles characterized by a variety of markers diagnostic of cancer. The data obtained from the MPNST and NF tissues was used as a training set (n=23) to develop the statistical model, yielding a sensitivity of 100.00%, specificity of 84.62%, and accuracy of 91.30%. The area under the curve (AUC) for the predictive model resulted in a value of 0.90. An additional statistical model was made comparing MPNST and normal tissue. Using a test set (n=21), we obtained a sensitivity of 100.00%, specificity of 81.82%, and accuracy of 90.48%, with an AUC of 0.88. Significance of microarrays (SAM) analysis to neurofibroma vs. MPNST and MPNST vs. normal tissue, found several m/z values downregulated in the NF and normal samples compared to the MPNST group. The three molecules with the largest differences indicated by the highest d score for the MPNST vs NF group were glycerophosphoserine (PS) 40:4 (m/z value 838.56), glycerophosphoethanolamine (PE) O-40:5 (m/z values 778.58 and 779.58), and glycerophosphoinositol (PI) 40:4 (m/z value 913.58). The three molecules with the largest differences indicated by the highest d score for the MPNST vs. normal tissue classification model were PE O-40:6 (m/z value 776.56), PE O-40:5 (m/z value 778.58), and PE O-38:5 / P-38:4 (m/z value 751.55).

Conclusions: We anticipate that the MasSpec Pen could transform NF1-associated MPNST treatment by increasing precision in diagnosis, margin evaluation, and expediting oncological surgeries.

Learning Objectives:

  • describe the need for rapid and accurate intraoperative margin assessment to guide extent of resection and surgical decision making.
  • interpret the accuracy of MasSpec Pen with regards to the successful identification of MPNST tumors samples over normal tissue controls.
  • describe the potential indications to use a technology such as MasSpec Pen to assess the presence of tumor within the surgical margin of the specimen.