Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance

被引:4
|
作者
Dundr, Pavel [1 ,2 ]
Hajkova, Nikola [1 ,2 ]
Bartu, Michaela Kendall [1 ,2 ]
Cibula, David [2 ,3 ]
Drozenova, Jana [4 ]
Fabian, Pavel [5 ]
Fadare, Oluwole [6 ]
Fruhauf, Filip [2 ,3 ]
Hausnerova, Jitka [7 ,8 ]
Hojny, Jan [1 ,2 ]
Laco, Jan [9 ,10 ]
Lax, Sigurd F. [11 ,12 ]
Matej, Radoslav [1 ,2 ,4 ,13 ]
Mehes, Gabor [14 ]
Michalkova, Romana [1 ,2 ]
Nemejcova, Kristyna [1 ,2 ]
Singh, Naveena [15 ]
Stolnicu, Simona [16 ]
Svajdler, Marian [17 ,18 ]
Zimas, Tomas [2 ,19 ]
McCluggage, W. Glenn [20 ]
Struzinska, Vana [1 ,2 ]
机构
[1] Charles Univ Prague, Fac Med 1, Dept Pathol, Studnickova 2, Prague 2, Czech Republic
[2] Gen Univ Hosp Prague, Studnickova 2, Prague 2, Czech Republic
[3] Charles Univ Prague, Fac Med 1, Dept Obstet & Gynecol, Prague, Czech Republic
[4] Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Dept Pathol, Prague, Czech Republic
[5] Masaryk Mem Canc Inst, Dept Oncol Pathol, Brno, Czech Republic
[6] Univ Calif San Diego, Dept Pathol, San Diego, CA USA
[7] Univ Hosp Brno, Dept Pathol, Brno, Czech Republic
[8] Masaryk Univ, Med Fac, Brno, Czech Republic
[9] Charles Univ Prague, Fac Med Hradec Kralove, Fingerland Dept Pathol, Hradec Kralove, Czech Republic
[10] Univ Hosp Hradec Kralove, Hradec Kralove, Czech Republic
[11] Gen Hosp Graz II, Dept Pathol, Graz, Austria
[12] Johannes Kepler Univ Linz, Linz, Austria
[13] Charles Univ Prague, Thomayer Univ Hosp, Fac Med 3, Dept Pathol & Mol Med, Prague, Czech Republic
[14] Univ Debrecen, Fac Med, Dept Pathol, Debrecen, Hungary
[15] Queen Mary Univ London, Barts Hlth NHS Trust, Blizard Inst Core Pathol, Dept Cellular Pathol, London, England
[16] George E Palade Univ Med Pharm Sci & Technol Targu, Dept Pathol, Targu Mures, Mures, Romania
[17] Charles Univ Prague, Fac Med, Sikls Dept Pathol, Plzen, Czech Republic
[18] Charles Univ Prague, Fac Hosp Pilsen, Plzen, Czech Republic
[19] Charles Univ Prague, Fac Med 1, Inst Med Biochem & Lab Diagnost, Prague, Czech Republic
[20] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, North Ireland
关键词
Mucinous tumours; ovary; p53; TP53; immunohistochemistry; next generation sequencing; GRADE SEROUS CARCINOMA; CANCER; SUBTYPES; PATHWAY; MARKERS; PROTEIN; UTILITY; CDKN2A; COMMON; STAGE;
D O I
10.1016/j.pathol.2023.04.008
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aber-rant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tu-mours (strong nuclear p53 staining in >12 consecutive tumour cells) and correlated the results with next genera-tion sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mu-tation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53 wild-type on sequencing. Three cases had normal p53 expression but contained a TP53 mutation. Overall, IHC predicted the TP53 mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predic-tive value of 92.7%. When comparing MC cases with wild-type TP53 versus those with TP53 mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in >= 12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53 mutation but the TP53 mutation status has no prognostic significance in either MC or MBT.
引用
收藏
页码:785 / 791
页数:7
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