Table 3 Overview of previously published studies on SPARC expression in PDAC
Author | Year | Clinical situation | Cases | Method | Antibody | Tissue type | Scoring method, stroma | Scoring method, cytoplasm | Cutoff | Stromal hi | Cytoplasmic hi | SPARC clinical relevance/conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Prenzel | 2006 | rPDAC | 31 | qPCR | NA | Snap-frozen fresh resection specimens | NA | NA | NA | NA | NA | No prognostic significance or association to clinicopathologic variables of SPARC mRNA expression was detected |
Infante | 2007 | rPDAC | 299 | IHC | Ms monoclonal clone ON-1, Zymed | Resection specimens TMA | Absent, weak (+), moderate (++), strong (+++) | Same as for stroma/not specified further | Negative: absent or weak in <10%; positive: moderate or strong in ⩾10% | 66.9% | 31.4% | SPARC expression in peritumoral fibroblasts was an independent prognostic biomarker, whereas tumoral SPARC expression was not |
Mantoni | 2008 | laPDAC | 58 | IHC | Ms monoclonal, Zymed | Biopsies whole mount | Combined semiquantitative score (intensity 0, 1, 2, 3) quantity (0=<5%, 1=5–25%, 2=26–50%, 3=>50%) | NA | Intensity 0 vs intensity 1–4 | NR | NR | SPARC expression in the stroma not directly adjacent to the tumour was a negative prognostic biomarker |
Miyoshi | 2010 | rPDAC | 104 | qPCR | NA | Resection specimens | NA | NA | NA | NA | NA | High SPARC mRNA level was an independent negative prognostic biomarker |
von Hoff | 2011 | mPDAC | 36 | IHC | One monoclonal and one polyclonal, not further specified | Not specified | Proprietary methodology: 7 tissue components evaluated (tumour, fibroblasts, immune cells, not further specified using two antibodies, each component three measures (maximum intensity, percentage at maximum intensity, overall score), resulting in 42 variables per tumour. Standardised via z-score and averaged between two observers. | NA | High SPARC: z-scores ⩾0; low SPARC: z-scores <0 | High SPARC 52.8% (according to z-score). Stromal or tumoral SPARC expression not reported separately | High SPARC (according to z-score) was a significant predictor for OS in nab-paclitaxel-treated patients. Stromal SPARC was significantly associated with OS but not SPARC in tumour cells | |
Sinn | 2014 | rPDAC | 160 | IHC | Ms monoclonal clone 15G12, Novocastra | Resection specimens TMA | Intensity (negative=0, weak=1, moderate=2, strong=3) | Percentage (0%=0–>80%=4) and intensity (0–3 as for stroma); multiplied to IRS 0–12 | Stroma: strong=strong; cytoplasm: IRS ⩾3=high | 58.1% | 26.3% | Strong stromal and high cytoplasmic SPARC expression were both associated with poor DFS and OS in pts treated with adjuvant gemcitabine |
Gundewar | 2014 | rPDAC | 88 | IHC | Ms monoclonal clone 15G12, Leica | Resection specimens type not specified | >10% considered positive, semiquantitative score for intensity (0=absent, 1=weak, 2=moderate, 3=strong) | NA | 0+1=low, 2+3=high | 15.9% | NR | High stromal SPARC expression was an independent negative prognostic biomarker. No association to type of CTX |
Hidalgo | 2015 | mPDAC | Stroma: 256; cytoplasm: 301 | IHC | Ms monoclonal clone ON-1, Invitrogen | Not specified | 0=absent, 1+=<25% positive at 200 × /400 ×, 2+=⩾25–49% positive at 100 × to 200 ×, 3+=⩾50% at 20 × to 40 × | H-score: % positive cells × staining intensity | Stroma: 3+=high, <3+=low; cytoplasm: H-score ⩾100=high, <100=low, absent=negative | 28.0% | 3.0% | High stromal and high cytoplasmic SPARC expression were not associated to OS in nab-paclitaxel- and gemcitabine-treated pts |
Ormanns | 2016 | laPDAC+mPDAC | 134 | IHC | Ms monoclonal clone ON-1, Invitrogen | Biopsies and resection specimens whole mount | Negative (low)=absent or weak in <25%; positive (high)=moderate to strong in ⩾25% | 0=absent, 1=faint or <10% positive, 2=weak in⩾10%, 3=moderate or strong in ⩾10% | Stroma: high vs low; cytoplasm: negative=0 or 1, positive=2 or 3 | 67.2% | 55.2% | Stromal SPARC expression was not associated to OS. Cytoplasmic SPARC expression was an independent predictor of poor PFS in the overall study population and of poor OS and PFS in the gemcitabine-based treated pts |
