BACKGROUND: Loss of mismatch repair (MMR) gene expression has been associated with fewer metastases and improved prognosis in various tumour types. AIMS: To evaluate the predictive and prognostic significance of loss of MMR protein MSH2 in early stage cervical cancer. METHODS: Specimens from 218 consecutive patients with early stage, surgically treated cervical cancer were analysed. Median age was 42 years (interquartile range 35-53). International Federation of Gynecology and Obstetrics (FIGO) stages were IB1 (57%), IB2 (25%) and IIA (18%). Histology was 70% squamous cell, 6% adenosquamous and 24% adenocarcinoma. Pelvic lymph node metastasis was present in 66 (30%) patients. Median follow-up was 5.2 years (interquartile range 2.5-7.9). Tissue microarrays (TMAs) were constructed containing three cores of paraffin-embedded tumour per case. MSH2 expression was assessed by immunohistochemistry on TMAs and full sections. RESULTS: In TMAs MSH2 expression could be analysed in 184/218 (84%) tumours. Loss of MSH2 was observed in 58/184 (32%) tumours, with a moderately strong concordance between TMAs and full sections (kappa = 0.47). In tumours with loss of MSH2, pelvic lymph node metastasis and cancer invasion beyond 10 mm were more frequent (48% vs 25%, and 59% vs 37%, respectively). However, loss of MSH2 expression was not related to recurrence or survival. CONCLUSION: TMAs are powerful tools for high throughput screening of biological markers for prognostic value in cervical cancer. Absence of MSH2 expression is associated with a high-risk profile in early stage cervical cancer, but does not predict lymph node status with sufficient accuracy to be used in the clinic.
BACKGROUND: Loss of mismatch repair (MMR) gene expression has been associated with fewer metastases and improved prognosis in various tumour types. AIMS: To evaluate the predictive and prognostic significance of loss of MMR protein MSH2 in early stage cervical cancer. METHODS: Specimens from 218 consecutive patients with early stage, surgically treated cervical cancer were analysed. Median age was 42 years (interquartile range 35-53). International Federation of Gynecology and Obstetrics (FIGO) stages were IB1 (57%), IB2 (25%) and IIA (18%). Histology was 70% squamous cell, 6% adenosquamous and 24% adenocarcinoma. Pelvic lymph node metastasis was present in 66 (30%) patients. Median follow-up was 5.2 years (interquartile range 2.5-7.9). Tissue microarrays (TMAs) were constructed containing three cores of paraffin-embedded tumour per case. MSH2 expression was assessed by immunohistochemistry on TMAs and full sections. RESULTS: In TMAsMSH2 expression could be analysed in 184/218 (84%) tumours. Loss of MSH2 was observed in 58/184 (32%) tumours, with a moderately strong concordance between TMAs and full sections (kappa = 0.47). In tumours with loss of MSH2, pelvic lymph node metastasis and cancer invasion beyond 10 mm were more frequent (48% vs 25%, and 59% vs 37%, respectively). However, loss of MSH2 expression was not related to recurrence or survival. CONCLUSION:TMAs are powerful tools for high throughput screening of biological markers for prognostic value in cervical cancer. Absence of MSH2 expression is associated with a high-risk profile in early stage cervical cancer, but does not predict lymph node status with sufficient accuracy to be used in the clinic.
Authors: G Bea A Wisman; Esther R Nijhuis; Mohammad O Hoque; Nathalie Reesink-Peters; Alice J Koning; Haukeline H Volders; Henk J Buikema; H Marike Boezen; Harry Hollema; Ed Schuuring; David Sidransky; Ate G J van der Zee Journal: Int J Cancer Date: 2006-10-15 Impact factor: 7.396
Authors: Yian Chen; Jiansong Wang; Mostafa M Fraig; Kelly Henderson; Nabil K Bissada; Dennis K Watson; Clifford W Schweinfest Journal: Int J Oncol Date: 2003-05 Impact factor: 5.650
Authors: M J Berends; H Hollema; Y Wu; T van Der Sluis; R G Mensink; K A ten Hoor; R H Sijmons; E G de Vries; E Pras; M J Mourits; R M Hofstra; C H Buys; J H Kleibeuker; A G van Der Zee Journal: Int J Cancer Date: 2001-05-01 Impact factor: 7.396
Authors: F S Leach; K Polyak; M Burrell; K A Johnson; D Hill; M G Dunlop; A H Wyllie; P Peltomaki; A de la Chapelle; S R Hamilton; K W Kinzler; B Vogelstein Journal: Cancer Res Date: 1996-01-15 Impact factor: 12.701
Authors: David Hardisson; Gema Moreno-Bueno; Lydia Sánchez; David Sarrió; Asunción Suárez; Francisco Calero; José Palacios Journal: Mod Pathol Date: 2003-11 Impact factor: 7.842