Expression of Metallothionein and Ki-67 Antigen in GISTs of Different Grade of Malignancy*

Abstract Background. Metallothioneins (MTs) are low molecular weight proteins (6-7 kDa), which have been shown to regulate zinc ion homeostasis. MTs exert anti-apoptotic and pro-proliferative effect on cancer cells. Overexpression of MT-I and MT-II isoforms has been noted in many malignant tumors, but the role of their expression in gastrointestinal stromal tumors (GISTs) remains unclear. Objectives. The aim of the study was to examine the relationship between expression of MT-I/II and K-67 proliferation antigen in a subset of GISTs presenting differential grade of malignancy. Material and Methods. The study was conducted using immunohistochemical methods on archival paraffin sections of 34 cases of GISTs. Of those, 17 tumors were classified as benign (GISTB) and 17 tumors as malignant (GISTM). Results. The GISTM cases demonstrated higher MT-I/II expression as compared to the GISTB cases, but not significantly higher (p = 0.08). The GISTM tumors showed significantly higher expression of Ki-67 antigen than the GISTB cases (p = 0.01). MT-I/II and Ki-67 expression positively correlated in GISTBs (r = 0.48, p = 0.0463), but not in GISTMs. Conclusion. The results of this study may point to a potential role of MT-I/II in the proliferation of GIST cells and disease progression (Adv Clin Exp Med 2013, 22, 4, 513-518)

Differential Expression of BARD1 Isoforms in Melanoma

Melanoma comprises <5% of cutaneous malignancies, yet it causes a significant proportion of skin cancer-related deaths worldwide. While new therapies for melanoma have been developed, not all patients respond well. Thus, further research is required to better predict patient outcomes. Using long-range nanopore sequencing, RT-qPCR, and RNA sequencing analyses, we examined the transcription of BARD1 splice isoforms in melanoma cell lines and patient tissue samples. Seventy-six BARD1 mRNA variants were identified in total, with several previously characterised isoforms (γ, φ, δ, ε, and η) contributing to a large proportion of the expressed transcripts. In addition, we identified four novel splice events, namely, Δ(E3_E9), ▼(i8), IVS10+131▼46, and IVS10▼176, occurring in various combinations in multiple transcripts. We found that short-read RNA-Seq analyses were limited in their ability to predict isoforms containing multiple non-contiguous splicing events, as compared to long-range nanopore sequencing. These studies suggest that further investigations into the functional significance of the identified BARD1 splice variants in melanoma are warranted