Browsing by Subject "survival"

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  • Tiihonen, R.; Alaranta, R.; Helkamaa, T.; Nurmi-Lüthje, I.; Kaukonen, J.-P.; Lüthje, P. (2019)
    Background and Aims: Reoperations after operative treatment of hip fracture patients may be associated with higher costs and inferior survival. We examined the acute hospital costs, long-term reoperation rates, and survival of patients with a new hip fracture. Materials and Methods: A total of 490 consecutive new hip fracture patients treated at a single center between 31 December 2004 and 6 December 2006 were analyzed retrospectively. Fractures were classified according to Garden and AO. All medical records were checked manually. The costs of reoperations were calculated using the diagnosis-related groups (DRG)-based prices. Survival analysis was performed using the life-table method. The follow-up time was 10 years. Results: In all, 70/490 patients (14.3%) needed reoperations. Of all reoperations, 34.2% were performed during the first month and 72.9% within 1 year after the primary operation. The hemiarthroplasty dislocation rate was 8.5%, and mechanical failures of osteosynthesis occurred in 6.2%. Alcohol abuse was associated with a heightened risk of reoperation. The mean direct costs of primary fracture care were lower than the mean costs of reoperations (euro7500 vs euro9800). The mortality rate at 10 years was 79.8% among non-reoperated patients and 62.9% among reoperated patients. Conclusions: According to our hypothesis, the cost per patient of reoperation in acute care was 31% higher than the corresponding cost of a primary operation. Reoperations increased the overall immediate costs of index fractures by nearly 20%. One-third of all reoperations were performed during the first month and almost 75% within 1 year after the primary operation.
  • Sundqvist, Benjamin; Kilpinen, Sami; Böhling, Tom; Koljonen, Virve; Sihto, Harri (2022)
    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 MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response. Conclusion: This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes.
  • Kaipio, Katja; Chen, Ping; Roering, Pia; Huhtinen, Kaisa; Mikkonen, Piia; Östling, Päivi; Lehtinen, Laura; Mansuri, Naziha; Korpela, Taina; Potdar, Swapnil; Hynninen, Johanna; Auranen, Annika; Grénman, Seija; Wennerberg, Krister; Hautaniemi, Sampsa; Carpén, Olli (2020)
    Poor chemotherapy response remains a major treatment challenge for high-grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient-derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment-naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment-naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment-naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K-mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K-mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment-naive tumours. EGFR, mTOR-PI3K and aurora kinase inhibitors are candidates for targeting this cell population. (c) 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
  • Mäkelä, Kati; Hodgson, Ulla; Piilonen, Anneli; Kelloniemi, Katariina; Bloigu, Risto; Sutinen, Eva; Salmenkivi, Kaisa; Rönty, Mikko; Lappi-Blanco, Elisa; Myllärniemi, Marjukka; Kaarteenaho, Riitta (Helsingin yliopisto, 2017)
    To be published later.
  • Zheng, Guoqiao; Chattopadhyay, Subhayan; Sundquist, Kristina; Sundquist, Jan; Forsti, Asta; Hemminki, Akseli; Hemminki, Kari (2020)
    The increased survival in malignant cutaneous melanoma (melanoma) is probably due to early diagnosis combined with improved treatment most recently. National health campaigns and screening programs for melanoma detection were started in Sweden several decades ago. We want to assess the influence of tumor characteristics, based on the TNM classification, and of second primary cancers on overall survival in melanoma. We used the Swedish Cancer Registry to assess all-cause survival in melanoma from 2003 to 2015. Hazard ratios (HRs) were estimated using multivariable Cox regression models. A total of 19,773 melanoma patients were diagnosed with TNM data. Survival showed a strong improving trend over time (p-trend
  • Tabarracci, Daniela Andrea (Helsingfors universitet, 2012)
    In 1987, the United Nations concerned with global challenges to human development called for a new model of growth to be erected upon the notion of sustainable development. Today, twenty five years later, the world continues to be beset by these global challenges and a governance gap around this issue has become manifest. Overtime, the international community came to the realization that, first, tackling these challenges requires the collective action of a multiplicity of relevant actors. And second, that the private sector, with its resources, know-how, experience and jurisdiction, could have a pivotal role to play to this end. The problem with these assumptions was the scepticism generated by mainstream interpretations of corporate nature and rationality. Despite the potential for contribution, corporations as self-interested agents in the struggle for the maximization of individual advantage could not be expected to contribute to the promotion of sustainable development; let alone through collective action. And yet contemporary evidence shows, that this scepticism is unwarranted. For that reason, the main purpose of this descriptive study was to account for the existing cases of collective action, and identify by listening to corporate actors, what was the rationale that underpinned their decisions to engage in these forms of collective action. In doing so, the aim was to assess the current suitability of mainstream approaches to reflect reality. Because of that, special attention was devoted to the notion of corporate self-interest (the key concept used by mainstream approaches to nurture the egoistic interpretation of the corporate actor). In listening to corporate actors two related qualitative analyses were conducted. On the one hand, a set of archival material - corporate responsibility reports and codes of conduct - was approached through a story-line narrative technique the purpose of which was to set the contextual and notional framework for the content analysis of interview transcripts that was to follow. On the other hand, semi-structured elite interviews were conducted on corporate executives of four transnational corporations, all of which are leaders in their respective industries and have a record of collective action that contributes to sustainable development. These corporations were Novartis, UPM, Tetra-Pak and Nokia and the overall purpose of the analytical chapter has been learn from corporate actors themselves what drove them to engage in these forms of collective action. At first glance the results of the analyses revealed that the rationale behind corporate engagement, continued to be explained by reference to corporate self-interest; just as mainstream approaches suggested. However, the point of divergence between these two interpretations was to be found in the way corporate self-interest was defined. According to mainstream approaches, corporate self-interest was defined in terms of profit maximization. Conversely, the findings unveiled in this study highlight the necessity to separate interests (instrumental reasons) from corporate self-interest (teleological reasons). In line with that differentiation, self-interest is defined as long-term survival, and all other interests are interpreted as instrumental to it. These findings have encouraging implications on the relevance of mainstream approaches to represent. Insofar a reassessment of the notion of corporate self-interest is undertaken to account for teleological reasons as distinct from instrumental reasons, mainstream approaches would be able to provide a fairer account of contemporary circumstances than they do today. In the absence of such an update, not only do they run the risk of not being able to reflect reality and becoming irrelevant, but they would also run the risk of rendering themselves unsuitable to account for changes in behaviours and interests, ultimately, downplaying rather than strengthening the rationality of actors. All in all, if what unrevised mainstream standards provide us with is an account for corporate rational behaviour, then what this study contributes is the possibility of moving past scepticism and understanding the potential for corporate behaviour to be better than rational.
  • Almangush, Alhadi; Leivo, Ilmo; Makitie, Antti A. (2021)
    Oral squamous cell carcinoma (OSCC) forms a major health problem in many countries. For several decades the management of OSCC consisted of surgery with or without radiotherapy or chemoradiotherapy. Aiming to increase survival rate, recent research has underlined the significance of harnessing the immune response in treatment of many cancers. The promising finding of checkpoint inhibitors as a weapon for targeting metastatic melanoma was a key event in the development of immunotherapy. Furthermore, clinical trials have recently proven inhibitor of PD-1 for treatment of recurrent/metastatic head and neck cancer. However, some challenges (including patient selection) are presented in the era of immunotherapy. In this mini-review we discuss the emergence of immunotherapy for OSCC and the recently introduced biomarkers of this therapeutic strategy. Immune biomarkers and their prognostic perspectives for selecting patients who may benefit from immunotherapy are addressed. In addition, possible use of such biomarkers to assess the response to this new treatment modality of OSCC will also be discussed.
  • Uusitalo, Elina; Kallionpaa, Roope A.; Kurki, Samu; Rantanen, Matti; Pitkaniemi, Janne; Kronqvist, Pauliina; Harkonen, Pirkko; Huovinen, Riikka; Carpen, Olli; Pöyhönen, Minna; Peltonen, Sirkku; Peltonen, Juha (2017)
    Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P = 0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1.
  • Franks, V. R.; Andrews, C. E.; Ewen, J. G.; McCready, M.; Parker, K. A.; Thorogood, R. (2020)
    Reintroductions, essential to many conservation programmes, disrupt both abiotic and social environments. Despite growing recognition that social connections in animals might alter survival (e.g. social transmission of foraging skills, or transmission of disease), there has thus far been little focus on the consequences of social disruption during reintroductions. Here we investigate if moving familiar social groups may help a threatened species to adjust to its new environment and increase post-release survival. For a reintroduction of 40 juvenile hihi Notiomystis cincta (a threatened New Zealand passerine), we observed social groups before and after translocation to a new site and used social network analysis to study three levels of social change: overall group structure, network associations and individual sociality. We also tested alternate translocation strategies where birds were kept temporarily in aviaries in either a familiar group, or where their prior association was mixed. Although social structure remained similar among juveniles that remained at the source site, we detected significant changes in translocated birds at both the group- and individual- level post-release. However, our holding treatments did not affect these social bonds so we remain unable to maintain or manipulate social groups during translocation. Crucially, there was a small tendency for translocated juveniles that gained more associates during re-assortment of social groups to be more likely to survive their first year post-release. We suggest that prior sociality may not be important during translocations, but rather individuals that are most able to adapt and form associations at a new site are most likely to be the surviving founders of reintroduced populations.
  • Vähämurto, Pauli; Mannisto, Susanna; Pollari, Marjukka; Karjalainen-Lindsberg, Marja-Liisa; Mäkitie, Antti A.; Leppä, Sirpa (2019)
    Purpose Sinonasal tract diffuse large B-cell lymphoma (SNT-DLBCL), a rare extranodal lymphoma, is not well characterized. We performed a population-based study to determine cell-of-origin, clinical presentation and impact of rituximab (R) and central nervous system (CNS) directed chemotherapy on survival. Patients and methods Patients with SNT-DLBCL were identified from pathology databases. Clinical information was collected and outcomes between different treatment modalities evaluated. Results Thirty-two percent of the patients had germinal centre B-cell phenotype. Forty-six patients were treated with curative intent using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like chemotherapy, 21 (46%) before and 25 (54%) in the R-era. Additionally, 24 (52%) received CNS-directed chemotherapy. Addition of R to chemotherapy reduced the risk of progression (RR = 0.368, 95% CI 0.138-0.976, P = 0.045) and death (RR = 0.245, 95% CI 0.068-0.883, P = 0.032), and translated into better survival (5-year PFS, 67% vs 38%, P = 0.037; 5-year OS, 81% vs 48%, P = 0.020). CNS-directed chemotherapy reduced the risk of progression (RR = 0.404, 95% CI 0.159-1.029, P = 0.057) and death (RR = 0.298, 95% CI 0.093-0.950, P = 0.041), and translated into favorable survival (5-year PFS, 67% vs 32%, P = 0.050; 5-year OS 82% vs 43%, P = 0.030). Conclusion Patients with SNT-DLBCL benefit from rituximab and CNS-directed chemotherapy.
  • Pulkka, Olli-Pekka; Mpindi, John-Patrick; Tynninen, Olli; Nilsson, Bengt; Kallioniemi, Olli; Sihto, Harri; Joensuu, Heikki (2018)
    The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4-related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST-specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
  • Relander, Kristiina; Hietanen, Marja; Nuotio, Krista; Ijäs, Petra; Tikkala, Irene; Saimanen, Eija; Lindsberg, Perttu J.; Soinne, Lauri (2021)
    Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival. Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders. Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8-13.9, p = 0.002) compared with patients with no cognitive decline. Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.
  • Karstunen, Emma (Helsingin yliopisto, 2017)
    Major extracardiac malformations are more common than previously 67 reported and found in 2/3 of cases with CDH and heart defect. Prenatal detection rates 68 for CDH and heart defects are low (49% and 41% respectively). The total prevalence of 69 UVH is 64 times higher and live birth prevalence 192 times higher than in general 70 population in Finland. The prognosis of CDH with major heart defects remains poor.
  • Dai, Xiaofeng; Li, Lu; Liu, Xiuxia; Hu, Weiguo; Yang, Yankun; Bai, Zhonghu (2015)
  • Boenink, Rianne; Stel, Vianda S.; Waldum-Grevbo, Bard E.; Collart, Frederic; Kerschbaum, Julia; Heaf, James G.; de Meester, Johan; Finne, Patrik; Garcia-Marcos, Sergio A.; Evans, Marie; Ambuhl, Patrice M.; Arici, Mustafa; Ayav, Carole; Steenkamp, Retha; Cases, Aleix; Traynor, Jamie P.; Palsson, Runolfur; Zoccali, Carmine; Massy, Ziad A.; Jager, Kitty J.; Kramer, Anneke (2020)
    The objective of this study was to investigate whether the improvement in survival seen in patients on kidney replacement therapy reflects the enhanced survival of the general population. Patient and general population statistics were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and the World Health Organization databases, respectively. Relative survival models were composed to examine trends over time in all-cause and cause-specific excess mortality, stratified by age and modality of kidney replacement therapy, and adjusted for sex, primary kidney disease and country. In total, 280,075 adult patients started kidney replacement therapy between 2002 and 2015. The excess mortality risk in these patients decreased by 16% per five years (relative excess mortality risk (RER) 0.84; 95% confidence interval 0.83-0.84). This reflected a 14% risk reduction in dialysis patients (RER 0.86; 0.85-0.86), and a 16% increase in kidney transplant recipients (RER 1.16; 1.07-1.26). Patients on dialysis showed a decrease in excess mortality risk of 28% per five years for atheromatous cardiovascular disease as the cause of death (RER 0.72; 0.70-0.74), 10% for non-atheromatous cardiovascular disease (RER 0.90; 0.88-0.92) and 10% for infections (RER 0.90; 0.87-0.92). Kidney transplant recipients showed stable excess mortality risks for most causes of death, although it did worsen in some subgroups. Thus, the increase in survival in patients on kidney replacement therapy is not only due to enhanced survival in the general population, but also due to improved survival in the patient population, primarily in dialysis patients.
  • Candolin, Ulrika; Goncalves, Sara; Pant, Pankaj (2022)
    Early life conditions can have a decisive influence on viability later in life. However, the influence of embryo density within a nest or body cavity on subsequent viability has received little attention within an ecological setting. This is surprising given that embryos often compete for limited resources, such as nutrients and oxygen, and this could influence their viability later in life through carry-over and compensatory effects. We show that the density of fertilized eggs within the nests of threespine stickleback males (Gasterosteus aculeatus) influences their viability after hatching. Embryos from larger broods hatch earlier and at a smaller size than those from smaller broods, which reduces their survival until the age of four weeks. This indicates a trade-off between the number and viability of offspring that males can raise to the hatching stage, which could explain the high incidence of partial egg cannibalism in nest-brooding fishes-as a strategy to improve the survival of remaining offspring. These results highlight the importance of considering conditions at the embryonic stage when evaluating the impact of early life conditions on viability and the adaptive value of reproductive decisions.
  • Helve, J; Kramer, A; Diez, JMA; Areste-Fosalba, N; Arici, M; Cases, A; Collart, F; Heaf, J; De Meester, J; Nordio, M; Palsson, R; Pobes, A; Rydell, H; Reisaeter, AV; Massy, ZA; Jager, KJ; Finne, P (2021)
    Background. The number of elderly patients on renal replacement therapy (RRT) is increasing. The survival and quality of life of these patients may be lower if they have multiple comorbidities at the onset of RRT. The aim of this study was to explore whether the effect of comorbidities on survival is similar in elderly RRT patients compared with younger ones. Methods. Included were 9333 patients >= 80years of age and 48352 patients 20-79 years of age starting RRT between 2010 and 2015 from 15 national or regional registries submitting data to the European Renal Association-European Dialysis and Transplantation Association Registry. Patients were followed until death or the end of 2016. Survival was assessed by Kaplan-Meier curves and the relative risk of death associated with comorbidities was assessed by Cox regression analysis. Results. Patients >= 80years of age had a greater comorbidity burden than younger patients. However, relative risks of death associated with all studied comorbidities (diabetes, ischaemic heart disease, chronic heart failure, cerebrovascular disease, peripheral vascular disease and malignancy) were significantly lower in elderly patients compared with younger patients. Also, the increase in absolute mortality rates associated with an increasing number of comorbidities was smaller in elderly patients. Conclusions. Comorbidities are common in elderly patients who enter RRT, but the risk of death associated with comorbidities is less than in younger patients. This should be taken into account when assessing the prognosis of elderly RRT patients.
  • Iivanainen, Sanna; Ahvonen, Jarkko; Knuuttila, Aija; Tiainen, Satu; Koivunen, Jussi Pekka (2019)
    Background Anti-PD-(L)1 agents are standard of care treatments in various cancers but predictive factors for therapy selection are limited. We hypothesised that markers of systemic inflammation would predict adverse outcomes in multiple cancers treated with anti-PD-(L)1 agents. Material and methods Discovery cohort consisted of patients who were treated with anti-programmed cell death protein-1 (PD-1) agents for advanced melanoma (MEL), non-small cell lung cancer (NSCLC) or renal and bladder cancers (GU) at Oulu University Hospital and had pretreatment C reactive protein (CRP), or neutrophil/lymphocyte values available. As a validation cohort, we collected patients treated with anti-PD-1 agents from three other hospitals in Finland. Results In the discovery cohort (n=56, MEL n=23, GU n=17, NSCLC n=16), elevated CRP over the upper limit of normal (ULN) (>10mg/mL) indicated poor progression-free (PFS; p=0.005) and overall survival (OS; p=0.000004) in the whole population and in MEL subgroup. Elevated neutrophil-to-lymphocyte ratio (>2.65) also indicated inferior PFS (p=0.02) and OS (p=0.009). In the validation cohort (n=107,MEL n=44, NSCLC n=42, GU n=17, other n=4), CRP over ULN also was a strong indicator for poor PFS (p=0.0000008), and OS (p=0.000006) in the whole population, and in MEL and NSCLC also. Conclusions Systemic inflammation suggested by elevated CRP is a very strong indicator for adverse prognosis on patients treated with anti-PD-(L)1 agents and has a potential negative predictive value for treatment with anti-PD-(L)1 agents. Prospective trials should investigate whether patients with elevated CRP gain any significant benefit from anti-PD-1 therapy.
  • Kiiski, Johanna; Fagerholm, Rainer; Tervasmaki, Anna; Pelttari, Liisa M.; Khan, Sofia; Jamshidi, Maral; Mantere, Tuomo; Pylkas, Katri; Bartek, Jiri; Bartkova, Jirina; Mannermaa, Arto; Tengstrom, Maria; Kosma, Veli-Matti; Winqvist, Robert; Kallioniemi, Anne; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli (2016)
    Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C> T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple-negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C> T mutation carriers and 3,832 non-carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C>T mutation associated with poor 10-year breast cancer-specific survival (hazard ratio (HR) 51.66, 95% confidence interval (CI) 1.09-2.52, p=0.018), with a more pronounced survival effect among familial cases (HR=2.93, 95% CI 1.5-5.76, p=1.80 x 10 23). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR=1.8, 95% CI 1.09-2.98, p=0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR=3.43, 95% CI 1.6-7.34, p=1.50x10(-3)) but not among radiotherapy treated patients (HR=1.35, 95% CI 0.82-2.23, p=0.237). Significant interaction was found between the mutation and radiotherapy (p=0.040). Immunohistochemical analyses show that c.5101C> T carriers have reduced PAR-activity. Our results suggest that FANCM c.5101C>T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage.
  • Sopyllo, Konrad; Erickson, Andrew M.; Mirtti, Tuomas (2021)
    Simple Summary Prostate cancer treatment decisions are based on clinical stage and histological diagnosis, including Gleason grading assessed by a pathologist, in biopsies. Prior to staging and grading, serum or blood prostate-specific antigen (PSA) levels are measured and often trigger diagnostic examinations. However, PSA is best suited as a marker of cancer relapse after initial treatment. In this review, we first narratively describe the evolution of histological grading, the current status of Gleason pattern-based diagnostics and glance into future methodology of risk assessment by histological examination. In the second part, we systematically review the biomarkers that have been shown, independent from clinical characteristics, to correlate with clinically relevant end-points, i.e., occurrence of metastases, disease-specific mortality and overall survival after initial treatment of localized prostate cancer. Gleason grading remains the strongest prognostic parameter in localized prostate adenocarcinoma. We have here outlined the evolution and contemporary practices in pathological evaluation of prostate tissue samples for Gleason score and Grade group. The state of more observer-independent grading methods with the aid of artificial intelligence is also reviewed. Additionally, we conducted a systematic review of biomarkers that hold promise in adding independent prognostic or predictive value on top of clinical parameters, Grade group and PSA. We especially focused on hard end points during the follow-up, i.e., occurrence of metastasis, disease-specific mortality and overall mortality. In peripheral blood, biopsy-detected prostate cancer or in surgical specimens, we can conclude that there are more than sixty biomarkers that have been shown to have independent prognostic significance when adjusted to conventional risk assessment or grouping. Our search brought up some known putative markers and panels, as expected. Also, the synthesis in the systematic review indicated markers that ought to be further studied as part of prospective trials and in well characterized patient cohorts in order to increase the resolution of the current clinico-pathological prognostic factors.