T. Merkx | Radboud University Nijmegen (original) (raw)

Papers by T. Merkx

Research paper thumbnail of Follow‐up after oral cancer treatment—Transition to a personalized approach

Journal of Oral Pathology & Medicine, 2021

BACKGROUND Guidelines for follow-up after oral cancer treatment are not site-specific and encompa... more BACKGROUND Guidelines for follow-up after oral cancer treatment are not site-specific and encompass the entire head and neck area rather than the oral cavity alone. This one-size-fits-all protocol disregards the differences in aetiology, treatment and differential distribution of new disease between the subsites. With the effectiveness of follow-up in early detection of new disease being put into question, the focus of follow-up programmes might shift to other aspects of survivorship care. Personalization of follow-up is important, considering patient-specific features and needs. Furthermore, the COVID-19 pandemic urges us to rethink our follow-up practice. FINDINGS This paper discusses ways in which routine follow-up in patients treated for oral cancer can be optimised. Patients with a high risk of new disease might benefit from an intensified follow-up regimen, whilst patients with a low risk of new disease, a low chance of cure or limited life expectancy could benefit from a de-intensified follow-up regimen. The latter could include a shorter follow-up period and focus on goals other than early detection of new disease. Education of patients to report new symptoms early is of vital importance as the majority of new disease presents symptomatically. Other health care professionals such as specialist nurses and dentists need to play an important leading role in survivorship care. Remote consultations may be useful to perform more efficient and patient centred follow-up care. CONCLUSION Routine follow-up needs to be seen as an integrated part of an individualized survivorship plan that is provided by the entire multidisciplinary team.

Research paper thumbnail of Multi-Center Validation of a Lymph Node Metastasis Gene-Expression Signature for Head and Neck Squamous Cell Carcinomas

Radiotherapy and Oncology, 2011

Otorhinolaryngolog

Research paper thumbnail of Toxicity and efficacy of accelerated radiotherapy with concurrent weekly cisplatin for locally advanced head and neck carcinoma

Head & neck, Apr 21, 2015

To report the results of accelerated radiotherapy with concomitant weekly cisplatin in head and n... more To report the results of accelerated radiotherapy with concomitant weekly cisplatin in head and neck cancer. One-hundred-and-six patients received concomitant cisplatin 40 mg/m(2) weekly with accelerated radiotherapy up to a dose of 68 Gy over 5.5 weeks. Ninety-nine percent of the patients received planned radiotherapy and 90% received ≥ 5 cycles of cisplatin. Moist desquamation of skin developed in 45% and confluent mucositis in 82%. Feeding tubes were required in 79% of the patients, and after 12 months in 4%. One patient developed nephrotoxicity. Three-year loco-regional control, disease-free survival and overall survival (OS) were 72%, 54% and 61%, respectively. HPV status was positive on PCR and p16in 11 of 50 tested oropharyngeal carcinoma (OPC) patients. Three-years OS was 81% and 66% in HPV-positive versus HPV-negative OPC patients (ns). Concomitant weekly cisplatin 40 mg/m(2) with accelerated radiotherapy was well tolerated and treatment compliance was high. This article i...

Research paper thumbnail of Het EPD als panacee voor problemen in de zorg?

Item does not contain fulltex

Research paper thumbnail of A Community-Based Oral Health Promotion Model for HIV Patients in Nairobi, East District in Kenya: A Study Protocol

Journal of Public Health Research, 2013

Background General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have a... more Background General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have a typical clinical appearance and can be recognised by members of the community. Although affected patients often experience pain leading to compromised eating and swallowing, barriers such as social stigma and lack of knowledge regarding available services may prevent them from seeking early care. Educating the community about these lesions through community health workers (CHWs) who are democratically elected community members may encourage individuals affected to seek early oral healthcare in the health facilities. A health facility (HF) is a health centre mainly run by clinical officers (CO), i.e. personnel with a 3-year medical training, and nurses. This study aims to evaluate the effect of a CHW training programme on: i) their knowledge and recognition of HIV-related oral-facial lesions at a community level; and ii) referral of affected patients from the community to the HFs. Design...

Research paper thumbnail of Cost‐effectiveness of selective neck dissection versus modified radical neck dissection for treating metastases in patients with oral cavity cancer: A modelling study

Head & Neck, 2015

ABSTRACTBackgroundChoosing between a more or less extensive neck dissection implies a tradeoff be... more ABSTRACTBackgroundChoosing between a more or less extensive neck dissection implies a tradeoff between survival, quality of life, and costs. The purpose of this study was to determine if selective neck dissection (level I–III or I–IV) is cost‐effective compared with modified radical neck dissection (level I–V) in patients with cT1–2 oral squamous cell carcinoma (OSCC) with singular nodal disease confined to level I or II.MethodsA decision‐analytic model was developed to model quality‐adjusted life years (QALYs) and costs over a lifetime horizon, based on literature.ResultsThe selective neck dissection strategy resulted in an expected health loss of 0.06 QALY and savings of €1351 per patient compared to modified radical neck dissection. The results were sensitive to differences in regional failure probabilities between the strategies.ConclusionWith the evidence used in this model, selective neck dissection was not cost‐effective compared to modified radical neck dissection. Prospecti...

Research paper thumbnail of OP176

Oral Oncology, 2013

Purpose Despite advances in surgical and other treatment modalities, the prognosis of patients wi... more Purpose Despite advances in surgical and other treatment modalities, the prognosis of patients with oral squamous cell carcinoma (OSCC) remains poor. It is well known that the early detection of OSCC and recurrent lesions is of utmost importance in obtaining disease control. Besides difficulty in visually differentiating between benign and (pre) cancerous lesions, the detection is hampered by the fact that scalpel biopsy is an invasive activity with potential morbidity. It is therefore not recommended to biopsy lesions on a regular basis. An easily performed, non-invasive screening method suitable to monitor lesions over time is urgently needed. In addition, the current histopathological examination suffers from inter- and intra-observer variability. In a previous study we showed the prognostic value of DNA image cytometry (ICM). Aim of the present study is assessment of the possibility to determine ploidy status using an oral brush. Materials and methods This prospective study included 85 (23 premalignancies, 27 stage T1 and 31 stage T2 OSCC) patients who visited the department of Oral and Maxillofacial Surgery at the Radboud University Nijmegen Medical Center, The Netherlands, with a suspected (pre) malignant lesion of the oral cavity. Newly discovered lesions as well as suspected recurrent OSCC were included. Both a brush and biopsy specimen were obtained for each patient. All specimens were analysed using ICM according to a well-established procedure. Results A significant difference was observed between brushes from diploid biopsies and brushes from non-diploid biopsies ( p Conclusions The oral brush biopsy is not suitable to replace the conventional surgical biopsy, however it may be of additional value in monitoring (pre) malignant lesions over time.

Research paper thumbnail of Rapid-growing Tumor of the Cheek Mimicking a Malignant Tumor

Journal of Pediatric Hematology/Oncology, 2011

In this case report, we describe a 5-month-old girl with a rapid-growing mass of the lower lip ex... more In this case report, we describe a 5-month-old girl with a rapid-growing mass of the lower lip extending to the buccal cheek. After surgical interference, the diagnosis lipoblastoma was made. Dealing with a fast-growing tumor in an infant, lipoblastic tumors belong in the differential diagnosis, however, a malignant process cannot be excluded. Rapid-growing lipoblastoma of infancy is a very rare benign tumor of embryonic white fatty cells. Magnetic resonance imaging might help with the diagnosis and often shows a lesion composed mostly, but not entirely, of fat. In this case report, we want to draw attention to the problems with diagnosis and therapeutic management of children with lipoblastoma.

Research paper thumbnail of Quantitative proteomics analysis reveals similar release profiles following specific PAR-1 or PAR-4 stimulation of platelets

Cardiovascular Research, 2014

Platelets are a natural source of growth factors, cytokines and chemokines, that regulate angioge... more Platelets are a natural source of growth factors, cytokines and chemokines, that regulate angiogenesis and inflammation. It has been suggested that differential release of pro-and anti-angiogenic growth factors from platelet a-granules by protease-activated receptors (PAR) 1 and 4 may be important for the regulation of angiogenesis. We aimed to compare the releasates of unstimulated platelets with PAR-1-and PAR-4-stimulated platelets. Methods and results The release of b-thromboglobulin, platelet factor (PF)-4, thrombospondin, platelet-derived growth factor (PDGF)-A/B, regulated and normal T-cell expressed and secreted (RANTES/CCL5), endostatin, CXCL12, and vascular endothelial growth factor (VEGF) was measured with enzyme-linked immunosorbent assay (ELISA). Mass spectrometry (MS)based quantitative proteomics identified 93 proteins from platelets stimulated with PAR-1 and PAR-4. A strong correlation between the factors released after either stimulus was observed (Spearman's r 0.94, P , 0.001). Analysis with ELISA showed that stimulation with PAR-1 or PAR-4 lead to non-differential release of b-thromboglobulin, PF-4, thrombospondin, PDGF-A/B, RANTES/CCL5, endostatin, CXCL12, and VEGF. Release of thrombospondin was slightly lower after PAR-1 stimulation (7.2 mg/mL), compared with PAR-4 induced release (9.8 mg/mL; P , 0.05). Conclusions Both ELISA on established a-granule proteins and MS-based quantitative proteomics showed that the most abundant agranule proteins are released in similar quantities from platelets after stimulation with either PAR-1 or PAR-4. Our findings provide evidence against the hypothesis that PAR-1 and PAR-4 stimulation of platelets trigger differential release of alpha-granule, but further studies are needed to draw conclusions for physiological conditions.

Research paper thumbnail of Koyio JPHR2012 1 e20(1)

Research paper thumbnail of Zonder tong geen leven : een hoofdhalszaak!

Niets uit deze uitgave mag worden vermenigvuldigd en/of openbaar worden gemaakt middels druk, fot... more Niets uit deze uitgave mag worden vermenigvuldigd en/of openbaar worden gemaakt middels druk, fotokopie, microfilm, geluidsband of op welke andere wijze dan ook, zonder voorafgaande schriftelijke toestemming van de copyrighthouder.

Research paper thumbnail of Treatment of oral cancer still reduce masticatory effectiveness: an opportunity for the orofacial physical therapist

Research paper thumbnail of A community-based oral health promotion model for HIV patients in Nairobi, East District in Kenya: a study protocol

Journal of Public Health Research, 2013

Background: General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have ... more Background: General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have a typical clinical appearance and can be recognised by members of the community. Although affected patients often experience pain leading to compromised eating and swallowing, barriers such as social stigma and lack of knowledge regarding available services may prevent them from seeking early care. Educating the community about these lesions through community health workers (CHWs) who are democratically elected community members may encourage individuals affected to seek early oral healthcare in the health facilities. A health facility (HF) is a health centre mainly run by clinical officers (CO), i.e. personnel with a 3-year medical training, and nurses. This study aims to evaluate the effect of a CHW training programme on: i) their knowledge and recognition of HIV-related oral-facial lesions at a community level; and ii) referral of affected patients from the community to the HFs.

Research paper thumbnail of Orofacial virtual mirror therapy

Research paper thumbnail of The declining role of surgery in the treatment of oral cancer?

International Journal of Oral and Maxillofacial Surgery, 2013

Research paper thumbnail of O92 The effect of hyperbaric oxygen therapy on quality of life in head and neck cancer patients treated with radiotherapy: a pilot study

Oral Oncology Supplement, 2007

Research paper thumbnail of Advantages of 3D planned mandibular reconstruction using a free vascularized fibular flap

International Journal of Oral and Maxillofacial Surgery, 2013

Research paper thumbnail of MULTI-CENTER VALIDATION OF A LYMPH NODE METASTASIS GENE-EXPRESSION SIGNATURE FOR HEAD AND NECK SQUAMOUS CELL CARCINOMAS

Radiotherapy and Oncology, 2011

Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinom... more Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinoma is not accurate enough to prevent overtreatment. The aim of this study was validation of a gene expression signature for distinguishing metastasizing (Nϩ) from nonmetastasizing (N0) squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC) in a large multicenter cohort, using a diagnostic DNA microarray in a Clinical Laboratory Improvement Amendments/ International Organization for Standardization-approved laboratory.

Research paper thumbnail of Follow‐up after oral cancer treatment—Transition to a personalized approach

Journal of Oral Pathology & Medicine, 2021

BACKGROUND Guidelines for follow-up after oral cancer treatment are not site-specific and encompa... more BACKGROUND Guidelines for follow-up after oral cancer treatment are not site-specific and encompass the entire head and neck area rather than the oral cavity alone. This one-size-fits-all protocol disregards the differences in aetiology, treatment and differential distribution of new disease between the subsites. With the effectiveness of follow-up in early detection of new disease being put into question, the focus of follow-up programmes might shift to other aspects of survivorship care. Personalization of follow-up is important, considering patient-specific features and needs. Furthermore, the COVID-19 pandemic urges us to rethink our follow-up practice. FINDINGS This paper discusses ways in which routine follow-up in patients treated for oral cancer can be optimised. Patients with a high risk of new disease might benefit from an intensified follow-up regimen, whilst patients with a low risk of new disease, a low chance of cure or limited life expectancy could benefit from a de-intensified follow-up regimen. The latter could include a shorter follow-up period and focus on goals other than early detection of new disease. Education of patients to report new symptoms early is of vital importance as the majority of new disease presents symptomatically. Other health care professionals such as specialist nurses and dentists need to play an important leading role in survivorship care. Remote consultations may be useful to perform more efficient and patient centred follow-up care. CONCLUSION Routine follow-up needs to be seen as an integrated part of an individualized survivorship plan that is provided by the entire multidisciplinary team.

Research paper thumbnail of Multi-Center Validation of a Lymph Node Metastasis Gene-Expression Signature for Head and Neck Squamous Cell Carcinomas

Radiotherapy and Oncology, 2011

Otorhinolaryngolog

Research paper thumbnail of Toxicity and efficacy of accelerated radiotherapy with concurrent weekly cisplatin for locally advanced head and neck carcinoma

Head & neck, Apr 21, 2015

To report the results of accelerated radiotherapy with concomitant weekly cisplatin in head and n... more To report the results of accelerated radiotherapy with concomitant weekly cisplatin in head and neck cancer. One-hundred-and-six patients received concomitant cisplatin 40 mg/m(2) weekly with accelerated radiotherapy up to a dose of 68 Gy over 5.5 weeks. Ninety-nine percent of the patients received planned radiotherapy and 90% received ≥ 5 cycles of cisplatin. Moist desquamation of skin developed in 45% and confluent mucositis in 82%. Feeding tubes were required in 79% of the patients, and after 12 months in 4%. One patient developed nephrotoxicity. Three-year loco-regional control, disease-free survival and overall survival (OS) were 72%, 54% and 61%, respectively. HPV status was positive on PCR and p16in 11 of 50 tested oropharyngeal carcinoma (OPC) patients. Three-years OS was 81% and 66% in HPV-positive versus HPV-negative OPC patients (ns). Concomitant weekly cisplatin 40 mg/m(2) with accelerated radiotherapy was well tolerated and treatment compliance was high. This article i...

Research paper thumbnail of Het EPD als panacee voor problemen in de zorg?

Item does not contain fulltex

Research paper thumbnail of A Community-Based Oral Health Promotion Model for HIV Patients in Nairobi, East District in Kenya: A Study Protocol

Journal of Public Health Research, 2013

Background General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have a... more Background General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have a typical clinical appearance and can be recognised by members of the community. Although affected patients often experience pain leading to compromised eating and swallowing, barriers such as social stigma and lack of knowledge regarding available services may prevent them from seeking early care. Educating the community about these lesions through community health workers (CHWs) who are democratically elected community members may encourage individuals affected to seek early oral healthcare in the health facilities. A health facility (HF) is a health centre mainly run by clinical officers (CO), i.e. personnel with a 3-year medical training, and nurses. This study aims to evaluate the effect of a CHW training programme on: i) their knowledge and recognition of HIV-related oral-facial lesions at a community level; and ii) referral of affected patients from the community to the HFs. Design...

Research paper thumbnail of Cost‐effectiveness of selective neck dissection versus modified radical neck dissection for treating metastases in patients with oral cavity cancer: A modelling study

Head & Neck, 2015

ABSTRACTBackgroundChoosing between a more or less extensive neck dissection implies a tradeoff be... more ABSTRACTBackgroundChoosing between a more or less extensive neck dissection implies a tradeoff between survival, quality of life, and costs. The purpose of this study was to determine if selective neck dissection (level I–III or I–IV) is cost‐effective compared with modified radical neck dissection (level I–V) in patients with cT1–2 oral squamous cell carcinoma (OSCC) with singular nodal disease confined to level I or II.MethodsA decision‐analytic model was developed to model quality‐adjusted life years (QALYs) and costs over a lifetime horizon, based on literature.ResultsThe selective neck dissection strategy resulted in an expected health loss of 0.06 QALY and savings of €1351 per patient compared to modified radical neck dissection. The results were sensitive to differences in regional failure probabilities between the strategies.ConclusionWith the evidence used in this model, selective neck dissection was not cost‐effective compared to modified radical neck dissection. Prospecti...

Research paper thumbnail of OP176

Oral Oncology, 2013

Purpose Despite advances in surgical and other treatment modalities, the prognosis of patients wi... more Purpose Despite advances in surgical and other treatment modalities, the prognosis of patients with oral squamous cell carcinoma (OSCC) remains poor. It is well known that the early detection of OSCC and recurrent lesions is of utmost importance in obtaining disease control. Besides difficulty in visually differentiating between benign and (pre) cancerous lesions, the detection is hampered by the fact that scalpel biopsy is an invasive activity with potential morbidity. It is therefore not recommended to biopsy lesions on a regular basis. An easily performed, non-invasive screening method suitable to monitor lesions over time is urgently needed. In addition, the current histopathological examination suffers from inter- and intra-observer variability. In a previous study we showed the prognostic value of DNA image cytometry (ICM). Aim of the present study is assessment of the possibility to determine ploidy status using an oral brush. Materials and methods This prospective study included 85 (23 premalignancies, 27 stage T1 and 31 stage T2 OSCC) patients who visited the department of Oral and Maxillofacial Surgery at the Radboud University Nijmegen Medical Center, The Netherlands, with a suspected (pre) malignant lesion of the oral cavity. Newly discovered lesions as well as suspected recurrent OSCC were included. Both a brush and biopsy specimen were obtained for each patient. All specimens were analysed using ICM according to a well-established procedure. Results A significant difference was observed between brushes from diploid biopsies and brushes from non-diploid biopsies ( p Conclusions The oral brush biopsy is not suitable to replace the conventional surgical biopsy, however it may be of additional value in monitoring (pre) malignant lesions over time.

Research paper thumbnail of Rapid-growing Tumor of the Cheek Mimicking a Malignant Tumor

Journal of Pediatric Hematology/Oncology, 2011

In this case report, we describe a 5-month-old girl with a rapid-growing mass of the lower lip ex... more In this case report, we describe a 5-month-old girl with a rapid-growing mass of the lower lip extending to the buccal cheek. After surgical interference, the diagnosis lipoblastoma was made. Dealing with a fast-growing tumor in an infant, lipoblastic tumors belong in the differential diagnosis, however, a malignant process cannot be excluded. Rapid-growing lipoblastoma of infancy is a very rare benign tumor of embryonic white fatty cells. Magnetic resonance imaging might help with the diagnosis and often shows a lesion composed mostly, but not entirely, of fat. In this case report, we want to draw attention to the problems with diagnosis and therapeutic management of children with lipoblastoma.

Research paper thumbnail of Quantitative proteomics analysis reveals similar release profiles following specific PAR-1 or PAR-4 stimulation of platelets

Cardiovascular Research, 2014

Platelets are a natural source of growth factors, cytokines and chemokines, that regulate angioge... more Platelets are a natural source of growth factors, cytokines and chemokines, that regulate angiogenesis and inflammation. It has been suggested that differential release of pro-and anti-angiogenic growth factors from platelet a-granules by protease-activated receptors (PAR) 1 and 4 may be important for the regulation of angiogenesis. We aimed to compare the releasates of unstimulated platelets with PAR-1-and PAR-4-stimulated platelets. Methods and results The release of b-thromboglobulin, platelet factor (PF)-4, thrombospondin, platelet-derived growth factor (PDGF)-A/B, regulated and normal T-cell expressed and secreted (RANTES/CCL5), endostatin, CXCL12, and vascular endothelial growth factor (VEGF) was measured with enzyme-linked immunosorbent assay (ELISA). Mass spectrometry (MS)based quantitative proteomics identified 93 proteins from platelets stimulated with PAR-1 and PAR-4. A strong correlation between the factors released after either stimulus was observed (Spearman's r 0.94, P , 0.001). Analysis with ELISA showed that stimulation with PAR-1 or PAR-4 lead to non-differential release of b-thromboglobulin, PF-4, thrombospondin, PDGF-A/B, RANTES/CCL5, endostatin, CXCL12, and VEGF. Release of thrombospondin was slightly lower after PAR-1 stimulation (7.2 mg/mL), compared with PAR-4 induced release (9.8 mg/mL; P , 0.05). Conclusions Both ELISA on established a-granule proteins and MS-based quantitative proteomics showed that the most abundant agranule proteins are released in similar quantities from platelets after stimulation with either PAR-1 or PAR-4. Our findings provide evidence against the hypothesis that PAR-1 and PAR-4 stimulation of platelets trigger differential release of alpha-granule, but further studies are needed to draw conclusions for physiological conditions.

Research paper thumbnail of Koyio JPHR2012 1 e20(1)

Research paper thumbnail of Zonder tong geen leven : een hoofdhalszaak!

Niets uit deze uitgave mag worden vermenigvuldigd en/of openbaar worden gemaakt middels druk, fot... more Niets uit deze uitgave mag worden vermenigvuldigd en/of openbaar worden gemaakt middels druk, fotokopie, microfilm, geluidsband of op welke andere wijze dan ook, zonder voorafgaande schriftelijke toestemming van de copyrighthouder.

Research paper thumbnail of Treatment of oral cancer still reduce masticatory effectiveness: an opportunity for the orofacial physical therapist

Research paper thumbnail of A community-based oral health promotion model for HIV patients in Nairobi, East District in Kenya: a study protocol

Journal of Public Health Research, 2013

Background: General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have ... more Background: General HIV-related orofacial lesions, most commonly oropharyngeal candidiasis, have a typical clinical appearance and can be recognised by members of the community. Although affected patients often experience pain leading to compromised eating and swallowing, barriers such as social stigma and lack of knowledge regarding available services may prevent them from seeking early care. Educating the community about these lesions through community health workers (CHWs) who are democratically elected community members may encourage individuals affected to seek early oral healthcare in the health facilities. A health facility (HF) is a health centre mainly run by clinical officers (CO), i.e. personnel with a 3-year medical training, and nurses. This study aims to evaluate the effect of a CHW training programme on: i) their knowledge and recognition of HIV-related oral-facial lesions at a community level; and ii) referral of affected patients from the community to the HFs.

Research paper thumbnail of Orofacial virtual mirror therapy

Research paper thumbnail of The declining role of surgery in the treatment of oral cancer?

International Journal of Oral and Maxillofacial Surgery, 2013

Research paper thumbnail of O92 The effect of hyperbaric oxygen therapy on quality of life in head and neck cancer patients treated with radiotherapy: a pilot study

Oral Oncology Supplement, 2007

Research paper thumbnail of Advantages of 3D planned mandibular reconstruction using a free vascularized fibular flap

International Journal of Oral and Maxillofacial Surgery, 2013

Research paper thumbnail of MULTI-CENTER VALIDATION OF A LYMPH NODE METASTASIS GENE-EXPRESSION SIGNATURE FOR HEAD AND NECK SQUAMOUS CELL CARCINOMAS

Radiotherapy and Oncology, 2011

Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinom... more Current assessment of lymph node metastasis in patients with head and neck squamous cell carcinoma is not accurate enough to prevent overtreatment. The aim of this study was validation of a gene expression signature for distinguishing metastasizing (Nϩ) from nonmetastasizing (N0) squamous cell carcinoma of the oral cavity (OSCC) and oropharynx (OPSCC) in a large multicenter cohort, using a diagnostic DNA microarray in a Clinical Laboratory Improvement Amendments/ International Organization for Standardization-approved laboratory.