Anti-KRT18 monoclonal antibody, clone Mu20.06

Background The most efficient treatment for cutaneous melanoma is surgical excision in its early stage, which involves an accurate differentiation between melanoma and atypical nevi. Objectives The aim of this study was to investigate the expression of GDF15, CYR61, KRT18 and BCL-2 in cutaneous melanoma, atypical nevi and common nevi and to assess their possible role in differentiating malignant and benign lesions. Material and Methods Tissues samples from 13 invasive cutaneous melanomas, 11 dysplastic nevi and 14 common nevi as well as ten normal skin tissue samples were used for gene expression analysis. Light Cycler 480 (Roche Technologies) and Delta Delta Ct methodwas used to evaluate the expression of genes of interest. Results Gene CYR 61 proved to be down-regulated in cutaneous melanoma and common melanocytic nevi and up-regulated in dysplastic melanocytic nevi. GDF15 expression is progressively up-regulated from common nevi to dysplastic nevi and melanoma. KRT18 is down-regulated in common nevi and melanoma, and is slightly up-regulated in dysplastic nevi. BCL2 expression is progressively down-regulated from common nevi to dysplastic nevi and melanoma. Conclusions GDF15 could represent an important factor for melanoma progression and for differential diagnosis. CYR61 seems to be an early marker of neoplasia, but its capacity to distinguish benign lesions from early malignant ones has to be tested on larger studies that also include in situ lesions. BCL2 does not seem to specifically contribute to differentiating benign lesions from malignant ones. KRT 18 could play a role in cell proliferation and distinguishing typical lesions from dysplastic ones.

To understand the molecular alterations driving the progression of ductal carcinoma in situ (DCIS), we compared patients with pure DCIS and patients with DCIS and synchronous invasive breast cancer (IBC). Twelve patients with extensive pure DCIS were included as a representation of indolent lesions with Limited invasive capacity. These cases were matched with 12 patients with a Limited DCIS component and IBC, representing lesions with a high invasive potential. Matching included age and surrogate DCIS subtypes. Gene expression profiling was performed on DCIS cells to identify transcriptional differences between these two groups. The identified genes were validated by immunohistochemistry. Nine genes showed significantly different expression. Most of these genes were highly expressed in DCIS samples with IBC, including PLAU (P = 0.002), COL1A1 (P = 0.006), KRT81 (P = 0.009), S100A7 (P = 0.015), SCGB1D2 (P = 0.023), KRT18 (P = 0.029), and NOTCH3 (P = 0.044), whereas EGFR and CXCL14 showed a higher expression in cases with pure DCIS (P = 0.015 and P = 0.028, respectively). This difference was only significant for SCGB1D2 (P = 0.009). Hierarchical clustering revealed distinct clustering of patients with and without invasion. Patients with pure DCIS have a different gene expression pattern as compared to patients with DCIS and synchronous IBC. These genes may pinpoint to driver pathway(s) that play an important role in DCIS progression.