Tom Böhling

University of Helsinki | HY · Department of Pathology

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...

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 tum...

Mixed neuroendocrine-non-neuroendocrine neoplasms (MINEN) are rare tumors that consist of at least 30% of both neuroendocrine and non-neuroendocrine components. The data concerning pathogenesis of MINEN suggest a monoclonal origin. We describe a spontaneously immortalized cell line derived from gastric MINEN called GNEN-1. Primary tumor consisted o...

Merkel cell carcinoma (MCC) is a rare skin cancer with only limited therapeutic options for advanced disease. We previously showed that oncogene ALK is frequently expressed at the RNA level in MCC and further that ALK positivity by immunohistochemistry is frequent and correlates strongly with Merkel cell polyomavirus (MCPyV) positivity. In this stu...

Background Radiation-associated angiosarcoma of the breast (RAASB) is a serious late consequence caused by breast cancer treatment. Initial symptoms are often inconspicuous, thus contributing to diagnostic delay. Most previous studies of the diagnostic aspects of RAASB are case reports. Purpose To perform a complete review of the imaging findings...

Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue cancer in need for novel therapies. Here we show that the PROX1 transcription factor, which is essential for normal myoblast differentiation, is highly expressed in RMS tumors. We demonstrate that PROX1 is needed for RMS cell stemness and growth in vitro, and for RMS tumor formation in m...

Malignant eccrine porocarcinoma is a rare skin adnexal cancer arising from the sweat glands. Little is known about the epidemiology and incidence of eccrine porocarcinoma. This registry-based study examined the epidemiology and incidence data for eccrine porocarcinoma from the Finnish Cancer Registry. The study included all persons diagnosed with e...

Background Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment. Methods A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify...

Background: Osteosarcomas (OS) in the craniomaxillofacial (CMF) region are typically diagnosed at later age than long-bone OS, but they are reported to have better 5-year survival. Curative treatment warrants wide surgical resection, which is often not possible in the CMF region. The purpose of this article is to present a nationwide series of CMF...

Background: Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protei...

A single-institution series using a (neo)adjuvant chemotherapy and interdigitated hyperfractionated split-course radiation therapy (CRT) treatment protocol for soft tissue sarcoma was reviewed. Our specific aims were to study recurrence rates and long-term toxicity. Between 1998 and 2016, 89 patients with non-metastatic soft tissue sarcoma were tre...

Aims Merkel cell carcinoma, a rare cutaneous neuroendocrine tumor of the skin, can be categorized into two groups according to Merkel cell polyomavirus (MCV) presence. MCV‐negative tumors are more aggressive and frequently associated with gene mutations. Some of the genes are potential therapeutic targets. We have previously reported EGFR mutations...

Background: Microbial ecosystems that inhabit the human gut form central component of our physiology and metabolism, regulating and modulating both health and disease. Changes or disturbances in the composition and activity of this gut microbiota can result in altered immunity, inflammation, and even cancer. Aim: To compare the composition and d...

Background Merkel cell carcinoma (MCC) tumor samples frequently express B‐lymphoid lineage markers. However, the reasons for expression of specific B‐lymphoid lineage markers are still unclear. We studied in a large pool of tissue microarray MCC samples, validate in a larger cohort the expression of TdT and Pax‐5, which are two B‐lymphoid lineage m...

Background: Genetic alterations occurring in lung cancer are the basis for defining molecular subtypes and essential for targeted therapies. Exhaled breath condensate (EBC) is a form of non-invasive sample that, amongst components, contains DNA from pulmonary tissue. Next-generation sequencing (NGS) was herein used to analyze mutations in EBC from...

Radiation‐associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population‐based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953‐2014 who were later diagnosed with a secondary sarcoma in 1953‐2014. Registry da...

Background and Objectives Desmoid tumors are soft‐tissue tumors originating from myofibroblasts with a tendency to recur after surgery. High expression of proliferation markers is associated with shortened progression‐free and/or overall survival in many neoplasms, including soft‐tissue sarcomas. We investigated the prognostic role of cyclin A and...

Introduction: The gut microbiome is a vital component of the gut environment regulating and modulating both health and disease. Disturbances in the microbiota can result in development of several types of gastrointestinal tract (GIT) malignancies either by the microbial metabolites or the pro-carcinogenic activities. Stool specimens represent a non...

Myxoinflammatory fibroblastic sarcoma is a soft-tissue neoplasm most frequently found in the distal extremities of middle-aged adults. Most myxoinflammatory fibroblastic sarcoma are low-grade tumors with propensity for local recurrence after incomplete removal. We report a myxoinflammatory fibroblastic sarcoma which developed in the foot of a 41-ye...

AIM To study cancer hotspot mutations by next-generation sequencing (NGS) in stool DNA from patients with different gastrointestinal tract (GIT) neoplasms. METHODS Stool samples were collected from 87 Finnish patients diagnosed with various gastric and colorectal neoplasms, including benign tumors, and from 14 healthy controls. DNA was isolated fr...

The two-stage induced-membrane technique for treatment of large bone defects has become popular among orthopedic surgeons. In the first operation, the bone defect is filled with poly(methyl methacrylate) (PMMA), which is intended to produce a membrane around the implant. In the second operation, PMMA is replaced with autograft or allograft bone. Bi...

Background Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA...

Background The primary neuroendocrine skin cancer, Merkel cell carcinoma (MCC), has a well-known predilection to metastasize systemically. However, the experience of systemic metastases in MCC is mainly disseminated through case reports due to the rarity of MCC. Purpose To elucidate the frequency and locations of systemic metastasis in MCC by revi...

Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to ide...

Background: We aimed to assess the connection between chronic inflammatory disorders (CIDs) and Merkel cell carcinoma (MCC). Methods: Merkel cell carcinoma cases diagnosed in 1978-2009 were extracted from the Finnish Cancer Registry and controls from the Population Registry. Information on reimbursed CIDs was linked to clinicopathological data i...

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognised neoplasm with a broad spectrum of morphological characteristics, thus representing a challenging differential diagnosis, especially with the low malignant potential multicystic renal cell neoplasms and clear cell renal cell carcinoma. We selected 14 cases of CCPRCC with a w...

Background and purpose — Soft-tissue sarcoma (STS) is rare, with challenging individualized treatment, so diagnostics and treatment should be centralized. Historical controls are sometimes used for investigation of whether new diagnostic or therapeutic tools affect patient outcome. However, as yet unknown factors may affect the outcome. We investig...

Malignant tumours are the foremost complications of immunosuppressive treatment. They are a major challenge for organ transplant recipients and their treating physicians. This paper reviews the aetiology and current treatment of an unusual neuroendocrine skin cancer, Merkel cell carcinoma (MCC), caused by a Merkel cell polyomavirus infection. MCC o...

Background: Mediator is a multiprotein interface between eukaryotic gene-specific transcription factors and RNA polymerase II. Mutations in exon 2 of the gene encoding MED12, a key subunit of the regulatory kinase module in Mediator, are extremely frequent in uterine leiomyomas, breast fibroadenomas, and phyllodes tumors. These mutations disrupt k...

EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility af...

We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). The study comprised of 128 patients with data on Merkel cell polyomavirus (MCV) status and clinical features were included in the study. I...

Merkel cell polyomavirus (MCV) is frequently detectable in Merkel cell carcinoma (MCC) tumors, but the significance of MCV infection is not yet totally understood. Thus far, no key regulatory miRNA has been identified for MCC tumorigenesis. However, distinct miRNA expression profiles have been suggested for MCV-positive and MCV-negative tumors. We...

Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operat...

Mediator regulates transcription by connecting gene-specific transcription factors to the RNA polymerase II initiation complex. We recently discovered by exome sequencing that specific exon 2 mutations in mediator complex subunit 12 (MED12) are extremely common in uterine leiomyomas. Subsequent screening studies have focused on this mutational hot...

Desmoid tumours are uncommon non-malignant tumours that show a locally aggressive growth pattern and a high local recurrence rate after surgery. Approximately 10% of the desmoid tumours are associated with familial adenomatous polyposis (FAP). Variable natural history of the disease challenges treatment decision-making in the absence of prospective...

Sequestration of the tumor suppressor retinoblastoma protein (RB) by the Merkel cell polyomavirus (MCV) is a crucial step in the pathogenesis of Merkel cell carcinoma (MCC). RB expression is frequently lost, particularly in MCV-negative MCC tumors, through yet unknown mechanisms. We compared the genomic copy number changes of 13 MCV-positive and 13...

Background: Prokineticin-1 (PROK1) and prokineticin-2 (PROK2) are chemokine-like proteins that may influence cancer growth by regulating host defence and angiogenesis. Their significance in viral infection-associated cancer is incompletely understood. We studied prokineticins in Merkel cell carcinoma (MCC), a skin cancer linked with Merkel cell pol...

Background: Most local recurrences have developed in the clinical target volume in previously published series after combined modality treatment for soft tissue sarcoma. However, marginal misses were seen in almost 20% of the patients. The aim of the present study was to determine the location of the recurrence and the total dose at the centre poi...

Renal cell carcinoma with prominent smooth muscle stroma is a rare neoplasm composed of an admixture of epithelial cell with clear cytoplasm arranged in small nest and tubular structures and a stroma composed of smooth muscle. In the epithelial component, loss of chromosome 3p detected by fluorescence in situ hybridization (FISH) has been reported...

The aim of this study was to compare three different methods to cover excised burn wounds in a randomized controlled trial. Fascially excised burn wounds, measuring 10cm×5cm, were covered with Integra(®), split thickness skin graft (STSG), and a viscose cellulose sponge Cellonex™ in each of ten adult patients. Integra(®) and Cellonex™ treated areas...

Abstract The purpose was to investigate the predictive power of sentinel lymph node biopsy (SLNB) in Merkel cell carcinoma (MCC) patients, using clinical data collected during treatment. The aim was also to review the treatment protocols for MCC patients in Finland. These data were retrieved and compared after identification in the Finnish Cancer R...

Background: Ewing's sarcoma family of tumors (ESFTs) are rare bone and soft tissue tumors characterized by specific genetic alterations. Our aim was to carry out a nationwide analysis of ESFT, to survey the treatments used and to report the five-year disease specific and event-free survival rates (EFS and DSS). Material and methods: The study da...

Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozyg...

Background: Mediator complex participates in transcriptional regulation by connecting regulatory DNA sequences to the RNA polymerase II initiation complex. Recently, we discovered through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined...

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma. The aims of this study were to investigate the expression of the transcription factors B-lymphoma Moloney murine leukaemia virus insertion (BMI1), myelocytomatosis viral oncogene homologue (c-Myc) and Snail in MCC tumour specimens and to examine the relationship of these mark...

Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine origin. The recently found Merkel cell polyomavirus (MCV) integrates clonally in the tumour genome, which suggests an important role in the pathogenesis of the disease. Previous small-scale studies have detected anti-apoptotic protein bcl-2 in 80 % of MCC tumours, but its...

Background The asymmetric laterality of UV-linked skin cancer, including melanoma and non- melanoma skin cancers has been identified. However, there seems to be a paucity in the data correlating the laterality and presence of Merkel cell polyoma virus (MCPyV) DNA as an aetiological factor for this phenomenon. Objective To study the laterality in Fi...

Merkel cell carcinoma (MCC) is a rare skin cancer that often harbors Merkel cell polyomavirus (MCPyV) DNA. The clinical importance of intratumoral immune cells and their associations with MCPyV infection are poorly understood. We identified T lymphocytes (CD3-positive cells), T-cell subsets (CD4, CD8, and FoxP3-positive cells), natural killer cells...

We developed a web-based, prognostic tool for extremity and trunk wall soft tissue sarcoma to predict 10-year sarcoma-specific survival. External validation was performed. Patients referred during 1987-2002 to Helsinki University Central Hospital are included. External validation was obtained from the Lund University Hospital register. Cox proporti...

A prospective diagnostics and treatment protocol for extremity and trunk wall soft tissue sarcoma (STS) was introduced by the Scandinavian Sarcoma Group in 1986 and it was also widely adopted in Finland. We have updated the protocol and made it more detailed at the Helsinki University Central Hospital. We retrospectively compared diagnostics and tr...

Radical surgery is not feasible for all osteosarcoma patients. Overall survival for non-extremity osteosarcoma, as well as for patients with metastatic disease at diagnosis remains poor. For such patients, radical radiotherapy combined with chemotherapy may present an effective treatment approach. This report describes the results of conservative t...

s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA Introduction: Merkel cell carcinoma (MCC) is rare and often aggressive skin cancer that manifests mainly in elderly white people. The majority of MCCs contain Merkel cell polyomavirus (MCPyV) DNA. Patients with MCPyV-positive M...

Patients diagnosed with osteosarcoma in Finland during 1991-2005 were retrospectively analyzed in a nationwide, population-based study. We focused on the incidence, treatment and outcome of osteosarcoma patients. We also evaluated the value of known prognostic parameters. Osteosarcomas were retrieved from the files of the national Finnish Cancer Re...

The aim of this study was to investigate the causes of death in patients with burns using both medicolegal autopsy reports and clinical data collected during treatment to specify irreversible organ dysfunctions leading to death. Burn deaths occurring in the Helsinki Burn Center from 1995 to 2005 were identified in the hospital database. The clinica...

Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause considerable morbidity. To study the genetic basis of this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED1...

Most Merkel cell carcinomas (MCCs) contain Merkel cell polyomavirus (MCPyV) DNA, and the virus likely has a pivotal role in tumor pathogenesis. p53 and the KIT receptor tyrosine kinase have also been implicated in MCC pathogenesis, but little is known about their association with MCPyV infection. We identified 207 patients diagnosed with MCC in Fin...

ZAC/PLAGL1 is a novel imprinted tumor suppressor gene encoding an important inducer of cell cycle arrest and apoptosis, and found to be lost during tumorigenesis. We analyzed the significance of ZAC in the development of a rare, usually benign tumor of the adrenal gland: pheochromocytoma (PCC). Twenty-four PCCs were analyzed for the loss of the act...