Merkel cell polyomavirus (MCPyV) is a causal factor in Merkel cell carcinoma (MCC). The oncogenic... more Merkel cell polyomavirus (MCPyV) is a causal factor in Merkel cell carcinoma (MCC). The oncogenic potential is mediated through its viral oncoproteins large T-antigen (LT) and small T-antigen (sT). Cytokines produced by tumor cells play an important role in cancer pathogenesis, and viruses affect their expression. Therefore, we compared human cytokine and receptor transcript levels in virus positive (V+) and virus negative (V−) MCC cell lines. Increased expression of IL-33, a potent modulator of tumor microenvironment, was observed in V+ MCC cell lines when compared to V− MCC-13 cells. Transient transfection studies with luciferase reporter plasmids demonstrated that LT and sT stimulated IL-33, ST2/IL1RL1 and IL1RAcP promoter activity. The induction of IL-33 expression was confirmed by transfecting MCC-13 cells with MCPyV LT. Furthermore, recombinant human cytokine domain IL-33 induced activation of MAP kinase and NF-κB pathways, which could be blocked by a ST2 receptor antibody. Im...
Eccrine porocarcinoma (EPC) is a rare malignant adnexal tumour of the skin. Part of EPCs develop ... more Eccrine porocarcinoma (EPC) is a rare malignant adnexal tumour of the skin. Part of EPCs develop from their benign counterpart, poroma (EP), with chronic light exposure and immunosuppression hypothesized to play a role in the malignant transformation. However, the impact of chronic light exposure on the microenvironment of EPCs and EPs has not been investigated yet. Although the clinical relevance of tumour infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) has been established in various tumours, their distribution and significance in EPCs and EPs is still poorly understood. We characterized the distribution of TILs and TLSs using CD3, CD4, CD8, CD20 immunohistochemistry in a cohort of 10 EPCs and 49 EPs. We then classified our samples using solar-elastosis grading, analyzing the influence of ultraviolet (UV) damage on TIL density. A negative correlation between UV damage and TIL density was observed (CD4 r = −0.286, p = 0.04. CD8 r = −0.305, p = 0.033). No sig...
Mikko Vuoristo , Timo Muhonen, Virve Koljonen, Susanna Juteau, Micaela Hernberg, Suvi Ilmonen and... more Mikko Vuoristo , Timo Muhonen, Virve Koljonen, Susanna Juteau, Micaela Hernberg, Suvi Ilmonen and Tiina Jahkola Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki, Helsinki, Finland; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Merkel cell polyomavirus (MCPyV) has been studied in several malignant and nonmalignant tissues. ... more Merkel cell polyomavirus (MCPyV) has been studied in several malignant and nonmalignant tissues. However, only in Merkel cell carcinoma (MCC) has the connection to tumorigenesis been established. Previously, eccrine porocarcinoma samples were shown to express MCPyV in the majority of samples. We aimed to examine MCPyV in porocarcinoma and poroma samples using MCC as the reference material.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The c... more Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The cell of origin of MCC is thus far unknown and proposed cells of origin include Merkel cells, pro-/pre- or pre-B cells, epithelial stem cells, and dermal stem cells. In this study, we aimed to shed further light on the possibility that a subset of MCC tumors arise from epithelial stem cells of the skin by examining the expression of hair follicle and epidermal stem cell markers in MCC and normal human skin. We also aimed to elucidate any correlation between the expression of these markers and tumor Merkel cell polyomavirus (MCPyV) status or other clinicopathological characteristics or patient survival. Expression of CK19, SOX9, LGR5, and LRIG1 in MCC and normal human skin was studied by immunohistochemistry, and the staining patterns or intensities were statistically correlated with patient, tumor, MCPyV, and survival parameters. In a cohort of 137 cases of MCC, we observed dot-like immuno...
Intimate partner violence (IPV) is a common cause of musculoskeletal injury. Although serious inj... more Intimate partner violence (IPV) is a common cause of musculoskeletal injury. Although serious injuries are relatively rare, IPV is one of the leading causes of homicide. IPV victims seeking help in health care are known to be at specific risk of re-abuse. Previous studies of IPV victims in emergency room (ER) settings have focused on injury patterns, but little is known about the violence behind bruises and fractures. The aim of this study was to examine how violence severity and known risk factors for lethal re-abuse in IPV victims attending ERs are associated with injury severity, different patient groups, and referral to advocacy services. This was a prospective, observational, multicenter study of 146 self-reporting IPV victims in two Level IV trauma centers in Helsinki from October 2012 to November 2013. In our sample, serious injuries were rare, but patients had typically suffered severe violence, and half had at least one risk factor for lethal re-abuse. Both sexes and all ag...
Merkel cell polyomavirus (MCV) infection underlies most Merkel cell carcinoma (MCC), a primary ne... more Merkel cell polyomavirus (MCV) infection underlies most Merkel cell carcinoma (MCC), a primary neuroendocrine carcinoma of the skin. While previous research has focused on MCV-positive MCC tumors, less is known about the oncogenesis in MCV-negative tumors. In this study, we analyzed mutational status of 27 MCC tumors with known MCV status for hotspot regions of 50 cancer-related genes by targeted next-generation sequencing using the Ion AmpliSeq Cancer Hotspot Panel. In addition to previously reported TP53, KIT, and PIK3CA gene mutations, we found somatic mutations in the tyrosine kinase domain of the EGFR gene in a small proportion of the cells in six tumor tissues. RB1 mutations were seen only in virus negative tumors. Hotspot mutations were more frequent in MCV-negative tumors, although the difference was not statistically significant. No clear hotspot mutation profile was observed. Novel RB1 mutations were detected only in MCV-negative tumors.
The great majority of chronic leg ulcers are caused by disturbances of venous and arterial circul... more The great majority of chronic leg ulcers are caused by disturbances of venous and arterial circulation in the lower extremities. Diagnostics and treatment of ulcers require multiprofessional collaboration. The cornerstone of the treatment is conservative treatment intervening in the underlying causes of the ulceration. If the ulcer is large or recovery does not take place with appropriate conservative therapy, reconstructive surgery may come into question, i.e. surgical excision of the ulcer and its covering with a skin graft.
Body piercing (BP) is defined as penetration of jewellery through the skin. Along with tattooing ... more Body piercing (BP) is defined as penetration of jewellery through the skin. Along with tattooing BPs are the most common body modifications. Complications related to piercing are numerous. They can be acute or chronic, infectious or non infectious and local or systemic complications. Acute infections constitute the most important complications and occur independently of the piercing site. Special attention should be brought on oral piercings, as they are frequent and responsible for numerous complications. A non-judgmental approach is recommended, when a pierced patient seeks medical help for a piercing complication or any other health issue.
The Journal of Trauma: Injury, Infection, and Critical Care, 2010
Background: We report microvascular free tissue transfers in pediatric patients in a retrospectiv... more Background: We report microvascular free tissue transfers in pediatric patients in a retrospective series. Methods: Forty-six children were treated in collaboration between the departments of Pediatric Surgery and Plastic Surgery, Helsinki University Hospital between 1986 and 2004 for microvascular free flap surgery. Trauma, tumor resection, congenital malformation, meningococcal septicaemia, and scars caused the tissue defects. The mean follow-up was 50 months. Results: The overall success rate was 96%. Twenty-five free flaps were transferred to the lower extremity. The most used flap was vascularized fibula. Preoperative angiography or intraoperative anticoagulants were not routinely used. Early reoperations were needed in four cases due to hematoma and in four cases due to thrombosis or impaired blood flow. All attempts of reanastomosis lead to salvage of the flap. Conclusion: In cases of severe tissue defects in pediatric patients, microvascular free flap reconstruction is a treatment of choice. A multicenter study for guidelines on preoperative assessment and antitrombotic therapy in pediatric microsurgery is warranted.
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society, 2022
In this editorial, we review our experience on distance teaching and based on our experiences sug... more In this editorial, we review our experience on distance teaching and based on our experiences suggest modifications to undergraduate surgical education.
Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma ... more Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes. Methods: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC. Results: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MC...
Moniammatillinen suunnittelu edistää melanoomapotilaan hoitoa Moniammatilliset ihokasvainkokoukse... more Moniammatillinen suunnittelu edistää melanoomapotilaan hoitoa Moniammatilliset ihokasvainkokoukset tuovat hoidon suunnitteluun monen erikoisalan asiantuntemuksen samanaikaisesti. Valtaosa tapauksista käsitellään lähetteiden ja potilasasiakirjojen perusteella, ja siksi hyvä lähete on erityisen tärkeä.
Lääkärillä on ammattinsa puolesta erityisiä velvoitteita. Hän päättää potilaan taudin määritykses... more Lääkärillä on ammattinsa puolesta erityisiä velvoitteita. Hän päättää potilaan taudin määrityksestä ja vastaa potilaan hoidosta (1). Sosiaalija terveysministeriön ohjeessa hoitotarvikkeiden ja -välineiden jakelusta todetaan seuraavaa: Tarvikkeiden ja välineiden jakamisen perusteena on ensinnäkin se, että jakelu perustuu aina yksiölliseen tarpeeseen, jonka määrittelee hoitava lääkäri. Jakelun aloittamisesta päättää terveys-
The Special Issue in Cancers, “The Biological and Clinical Aspects of Merkel Cell Carcinoma”, wal... more The Special Issue in Cancers, “The Biological and Clinical Aspects of Merkel Cell Carcinoma”, walks the avid reader through the interesting and sometimes even mysterious facets of Merkel cell carcinoma (MCC), starting at its carcinogenesis to also cover innovative treatment options [...]
Journal of Plastic, Reconstructive & Aesthetic Surgery, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Merkel cell polyomavirus (MCPyV) is a causal factor in Merkel cell carcinoma (MCC). The oncogenic... more Merkel cell polyomavirus (MCPyV) is a causal factor in Merkel cell carcinoma (MCC). The oncogenic potential is mediated through its viral oncoproteins large T-antigen (LT) and small T-antigen (sT). Cytokines produced by tumor cells play an important role in cancer pathogenesis, and viruses affect their expression. Therefore, we compared human cytokine and receptor transcript levels in virus positive (V+) and virus negative (V−) MCC cell lines. Increased expression of IL-33, a potent modulator of tumor microenvironment, was observed in V+ MCC cell lines when compared to V− MCC-13 cells. Transient transfection studies with luciferase reporter plasmids demonstrated that LT and sT stimulated IL-33, ST2/IL1RL1 and IL1RAcP promoter activity. The induction of IL-33 expression was confirmed by transfecting MCC-13 cells with MCPyV LT. Furthermore, recombinant human cytokine domain IL-33 induced activation of MAP kinase and NF-κB pathways, which could be blocked by a ST2 receptor antibody. Im...
Eccrine porocarcinoma (EPC) is a rare malignant adnexal tumour of the skin. Part of EPCs develop ... more Eccrine porocarcinoma (EPC) is a rare malignant adnexal tumour of the skin. Part of EPCs develop from their benign counterpart, poroma (EP), with chronic light exposure and immunosuppression hypothesized to play a role in the malignant transformation. However, the impact of chronic light exposure on the microenvironment of EPCs and EPs has not been investigated yet. Although the clinical relevance of tumour infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) has been established in various tumours, their distribution and significance in EPCs and EPs is still poorly understood. We characterized the distribution of TILs and TLSs using CD3, CD4, CD8, CD20 immunohistochemistry in a cohort of 10 EPCs and 49 EPs. We then classified our samples using solar-elastosis grading, analyzing the influence of ultraviolet (UV) damage on TIL density. A negative correlation between UV damage and TIL density was observed (CD4 r = −0.286, p = 0.04. CD8 r = −0.305, p = 0.033). No sig...
Mikko Vuoristo , Timo Muhonen, Virve Koljonen, Susanna Juteau, Micaela Hernberg, Suvi Ilmonen and... more Mikko Vuoristo , Timo Muhonen, Virve Koljonen, Susanna Juteau, Micaela Hernberg, Suvi Ilmonen and Tiina Jahkola Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki, Helsinki, Finland; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Merkel cell polyomavirus (MCPyV) has been studied in several malignant and nonmalignant tissues. ... more Merkel cell polyomavirus (MCPyV) has been studied in several malignant and nonmalignant tissues. However, only in Merkel cell carcinoma (MCC) has the connection to tumorigenesis been established. Previously, eccrine porocarcinoma samples were shown to express MCPyV in the majority of samples. We aimed to examine MCPyV in porocarcinoma and poroma samples using MCC as the reference material.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The c... more Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The cell of origin of MCC is thus far unknown and proposed cells of origin include Merkel cells, pro-/pre- or pre-B cells, epithelial stem cells, and dermal stem cells. In this study, we aimed to shed further light on the possibility that a subset of MCC tumors arise from epithelial stem cells of the skin by examining the expression of hair follicle and epidermal stem cell markers in MCC and normal human skin. We also aimed to elucidate any correlation between the expression of these markers and tumor Merkel cell polyomavirus (MCPyV) status or other clinicopathological characteristics or patient survival. Expression of CK19, SOX9, LGR5, and LRIG1 in MCC and normal human skin was studied by immunohistochemistry, and the staining patterns or intensities were statistically correlated with patient, tumor, MCPyV, and survival parameters. In a cohort of 137 cases of MCC, we observed dot-like immuno...
Intimate partner violence (IPV) is a common cause of musculoskeletal injury. Although serious inj... more Intimate partner violence (IPV) is a common cause of musculoskeletal injury. Although serious injuries are relatively rare, IPV is one of the leading causes of homicide. IPV victims seeking help in health care are known to be at specific risk of re-abuse. Previous studies of IPV victims in emergency room (ER) settings have focused on injury patterns, but little is known about the violence behind bruises and fractures. The aim of this study was to examine how violence severity and known risk factors for lethal re-abuse in IPV victims attending ERs are associated with injury severity, different patient groups, and referral to advocacy services. This was a prospective, observational, multicenter study of 146 self-reporting IPV victims in two Level IV trauma centers in Helsinki from October 2012 to November 2013. In our sample, serious injuries were rare, but patients had typically suffered severe violence, and half had at least one risk factor for lethal re-abuse. Both sexes and all ag...
Merkel cell polyomavirus (MCV) infection underlies most Merkel cell carcinoma (MCC), a primary ne... more Merkel cell polyomavirus (MCV) infection underlies most Merkel cell carcinoma (MCC), a primary neuroendocrine carcinoma of the skin. While previous research has focused on MCV-positive MCC tumors, less is known about the oncogenesis in MCV-negative tumors. In this study, we analyzed mutational status of 27 MCC tumors with known MCV status for hotspot regions of 50 cancer-related genes by targeted next-generation sequencing using the Ion AmpliSeq Cancer Hotspot Panel. In addition to previously reported TP53, KIT, and PIK3CA gene mutations, we found somatic mutations in the tyrosine kinase domain of the EGFR gene in a small proportion of the cells in six tumor tissues. RB1 mutations were seen only in virus negative tumors. Hotspot mutations were more frequent in MCV-negative tumors, although the difference was not statistically significant. No clear hotspot mutation profile was observed. Novel RB1 mutations were detected only in MCV-negative tumors.
The great majority of chronic leg ulcers are caused by disturbances of venous and arterial circul... more The great majority of chronic leg ulcers are caused by disturbances of venous and arterial circulation in the lower extremities. Diagnostics and treatment of ulcers require multiprofessional collaboration. The cornerstone of the treatment is conservative treatment intervening in the underlying causes of the ulceration. If the ulcer is large or recovery does not take place with appropriate conservative therapy, reconstructive surgery may come into question, i.e. surgical excision of the ulcer and its covering with a skin graft.
Body piercing (BP) is defined as penetration of jewellery through the skin. Along with tattooing ... more Body piercing (BP) is defined as penetration of jewellery through the skin. Along with tattooing BPs are the most common body modifications. Complications related to piercing are numerous. They can be acute or chronic, infectious or non infectious and local or systemic complications. Acute infections constitute the most important complications and occur independently of the piercing site. Special attention should be brought on oral piercings, as they are frequent and responsible for numerous complications. A non-judgmental approach is recommended, when a pierced patient seeks medical help for a piercing complication or any other health issue.
The Journal of Trauma: Injury, Infection, and Critical Care, 2010
Background: We report microvascular free tissue transfers in pediatric patients in a retrospectiv... more Background: We report microvascular free tissue transfers in pediatric patients in a retrospective series. Methods: Forty-six children were treated in collaboration between the departments of Pediatric Surgery and Plastic Surgery, Helsinki University Hospital between 1986 and 2004 for microvascular free flap surgery. Trauma, tumor resection, congenital malformation, meningococcal septicaemia, and scars caused the tissue defects. The mean follow-up was 50 months. Results: The overall success rate was 96%. Twenty-five free flaps were transferred to the lower extremity. The most used flap was vascularized fibula. Preoperative angiography or intraoperative anticoagulants were not routinely used. Early reoperations were needed in four cases due to hematoma and in four cases due to thrombosis or impaired blood flow. All attempts of reanastomosis lead to salvage of the flap. Conclusion: In cases of severe tissue defects in pediatric patients, microvascular free flap reconstruction is a treatment of choice. A multicenter study for guidelines on preoperative assessment and antitrombotic therapy in pediatric microsurgery is warranted.
Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society, 2022
In this editorial, we review our experience on distance teaching and based on our experiences sug... more In this editorial, we review our experience on distance teaching and based on our experiences suggest modifications to undergraduate surgical education.
Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma ... more Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes. Methods: We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC. Results: We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MC...
Moniammatillinen suunnittelu edistää melanoomapotilaan hoitoa Moniammatilliset ihokasvainkokoukse... more Moniammatillinen suunnittelu edistää melanoomapotilaan hoitoa Moniammatilliset ihokasvainkokoukset tuovat hoidon suunnitteluun monen erikoisalan asiantuntemuksen samanaikaisesti. Valtaosa tapauksista käsitellään lähetteiden ja potilasasiakirjojen perusteella, ja siksi hyvä lähete on erityisen tärkeä.
Lääkärillä on ammattinsa puolesta erityisiä velvoitteita. Hän päättää potilaan taudin määritykses... more Lääkärillä on ammattinsa puolesta erityisiä velvoitteita. Hän päättää potilaan taudin määrityksestä ja vastaa potilaan hoidosta (1). Sosiaalija terveysministeriön ohjeessa hoitotarvikkeiden ja -välineiden jakelusta todetaan seuraavaa: Tarvikkeiden ja välineiden jakamisen perusteena on ensinnäkin se, että jakelu perustuu aina yksiölliseen tarpeeseen, jonka määrittelee hoitava lääkäri. Jakelun aloittamisesta päättää terveys-
The Special Issue in Cancers, “The Biological and Clinical Aspects of Merkel Cell Carcinoma”, wal... more The Special Issue in Cancers, “The Biological and Clinical Aspects of Merkel Cell Carcinoma”, walks the avid reader through the interesting and sometimes even mysterious facets of Merkel cell carcinoma (MCC), starting at its carcinogenesis to also cover innovative treatment options [...]
Journal of Plastic, Reconstructive & Aesthetic Surgery, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Uploads
Papers by Virve Koljonen