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. 2019 May 10;3(5):646-655.
doi: 10.1002/bjs5.50175. eCollection 2019 Oct.

Prognostic impact of Ki-67 proliferative index in resectable pancreatic ductal adenocarcinoma

I Pergolini  1 , S Crippa  2 , M Pagnanelli  2 , G Belfiori  1 , A Pucci  1 , S Partelli  2 , C Rubini  3 , P Castelli  4 , G Zamboni  4   5 , M Falconi  2
Affiliations

Prognostic impact of Ki-67 proliferative index in resectable pancreatic ductal adenocarcinoma

I Pergolini et al. BJS Open. .

Abstract
in English, Spanish

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by complex biological features and poor prognosis. A prognostic stratification of PDAC would help to improve patient management. The aim of this study was to analyse the expression of Ki-67 in relation to prognosis in a cohort of patients with PDAC who had surgical treatment.

Methods: Patients who had pancreatic resection between August 2010 and October 2014 for PDAC at two Italian centres were reviewed retrospectively. Patients with metastatic or locally advanced disease, those who received neoadjuvant chemotherapy, patients with PDAC arising from intraductal papillary mucinous neoplasm and those with missing data were excluded. Clinical and pathological data were retrieved and analysed. Ki-67 expression was evaluated using immunohistochemistry and patients were stratified into three subgroups. Survival analyses were performed for disease-free (DFS) and disease-specific (DSS) survival outcomes according to Ki-67 expression and tumour grading.

Results: A total of 170 patients met the selection criteria. Ki-67 expression of 10 per cent or less, 11-50 per cent and more than 50 per cent significantly correlated with DFS and DSS outcomes (P = 0·016 and P = 0·002 respectively). Ki-67 index was an independent predictor of poor DFS (hazard ratio (HR) 0·52, 95 per cent c.i. 0·29 to 0·91; P = 0·022) and DSS (HR 0·53, 0·31 to 0·91; P = 0·022). Moreover, Ki-67 index correlated strongly with tumour grade (P < 0·001). Patients with PDAC classified as a G3 tumour with a Ki-67 index above 50 per cent had poor survival outcomes compared with other patients (P < 0·001 for both DFS and DSS).

Conclusion: Ki-67 index could be of use in predicting the survival of patients with PDAC. Further investigation in larger cohorts is needed to validate these results.

Antecedentes: El adenocarcinoma ductal de páncreas (pancreatic ductal adenocarcinoma, PDAC) es una enfermedad agresiva con características biológicas complejas y pronóstico pobre. La estratificación pronóstica del PDAC ayudaría a mejorar el tratamiento del paciente. El objetivo de este estudio era analizar la expresión de Ki‐67 como marcador pronóstico en una cohorte de pacientes con PDAC tratados quirúrgicamente.

Métodos: Se efectuó un análisis retrospectivo de pacientes sometidos a resección pancreática por PDAC en dos centros italianos entre agosto de 2010 y octubre de 2014. Se excluyeron los pacientes con enfermedad metastásica o localmente avanzada, los tratados con quimioterapia neoadyuvante, los pacientes con PDAC originado en una neoplasia papilar mucinosa intraductal y aquellos pacientes con datos incompletos. Se analizaron los datos clínicos y anatomopatológicos. La expresión de Ki‐67 se evaluó por inmunohistoquímica y los pacientes se estratificaron en tres grupos. Se calculó la supervivencia libre de enfermedad (disease‐free survival, DFS) y la supervivencia específica de la enfermedad (disease‐specific survival, DSS) según la expresión de Ki‐67 y el grado tumoral.

Resultados: Un total de 170 pacientes cumplió los criterios de selección. La expresión de Ki‐67 del ≤ 10%, 11‐50% y > 50% mostró una correlación significativa con los resultados de DFS y DSS (P = 0,016 y P = 0,002, respectivamente). El índice Ki‐67 fue un predictor independiente de pobre DFS (cociente de riesgos instantáneos, hazard ratio, HR 0,52, i.c. del 95% 0,29‐0,91; P = 0,022) y DSS (HR 0,53, i.c. del 95% 0,31‐0,91; P = 0,022). Asimismo, el índice Ki‐67 se correlacionaba fuertemente con el grado tumoral (P < 0,001). Los pacientes con un PDAC clasificado como tumor grado G3 y con un índice Ki‐67 > 50% tenían peores resultados de supervivencia en comparación con otros pacientes (P < 0,001 para ambos DFS y DSS).

Conclusión: El índice Ki‐67 se puede utilizar como predictor de supervivencia en pacientes con PDAC. Hace falta seguir investigando para validar estos resultados en cohortes más grandes.

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Figures

Figure 1
Figure 1
Kaplan–Meier analysis of survival in Ki‐67 index subgroups. a Disease‐free (DFS) and b disease‐specific (DSS) survival in patients with a Ki‐67 index of 10 per cent or less, 11–50 per cent and more than 50 per cent. a P = 0·016, b P = 0·002 (log rank test)
Figure 2
Figure 2
Box‐and‐whisker plot of Ki‐67 index according to tumour grade of differentiation. Median Ki‐67 index values, interquartile ranges and ranges are denoted by horizontal bars, boxes and error bars respectively. P < 0·001 (Kruskal–Wallis test)
Figure 3
Figure 3
Ki‐67 immunohistochemical staining in pancreatic ductal adenocarcinoma. a G1 tumour with Ki‐67 index of 10 per cent or less; b G2 tumour with Ki‐67 index of 11–50 per cent; c G3 tumour with Ki‐67 index above 50 per cent
Figure 4
Figure 4
Kaplan–Meier analysis of survival according to Ki‐67 and tumour grade. a Disease‐free (DFS) and b disease‐specific (DSS) survival in patients with G1 tumours and Ki‐67 index of 10 per cent or less (group 1), G3 tumours and Ki‐67 index above 50 per cent (group 2), and all other patients (G1 tumours and Ki‐67 index above 10 per cent, G2 tumours with any Ki‐67 value and G3 tumours with Ki‐67 index of 50 per cent or less) (group 3). a,b P < 0·001 (log rank test)
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