Osteopontin expression in Osteopontin expression in salivary gland cancersalivary gland cancer

Kristine Bjørndal, Christian Godballe, Kristine Bjørndal, Christian Godballe, Jørgen Johansen, Jens Overgaard, Jørgen Johansen, Jens Overgaard,

Annelise KrogdahlAnnelise Krogdahl

Odense University Hospital, DKOdense University Hospital, DK

Aim of the studyAim of the study

ToTo evaluate osteopontin evaluate osteopontin expression and its prognostic expression and its prognostic information in salivary gland information in salivary gland

cancercancer

MaterialMaterial

• Salivary gland carcinomas treated at Odense Salivary gland carcinomas treated at Odense University HospitalUniversity Hospital

• 1990-20051990-2005• 48% males and 52% females48% males and 52% females• Clinical data retrieved from the national Clinical data retrieved from the national

database DASPYTCAdatabase DASPYTCA• Immunohistochemical investigations performed Immunohistochemical investigations performed

on surgical specimens on surgical specimens • Revision Revision

MaterialMaterial

199 patients199 patients3 – records 3 before 19903 – records 3 before 1990

5 metastases 10 - tumor5 metastases 10 - tumor

1 – follow-up 3 changed 1 – follow-up 3 changed diagnosisdiagnosis 174 patients174 patients (OPN + follow-up)(OPN + follow-up)

Number of coloured tumor cellsNumber of coloured tumor cells

• 0=none0=none• 1=<1/1001=<1/100• 2=1/100-1/10 2=1/100-1/10 • 3=1/10-1/33=1/10-1/3• 4=1/3-2/34=1/3-2/3• 5=>2/35=>2/3

0

10

20

30

40

50

60

70

80

90

0 1 2 3 4 5

Coloured tumorcells

%All salivary gland carcinomas stain. In 87% over

2/3 of the tumor cells are coloured

NO CUT POINT

Colour intensityColour intensity

0

5

10

15

20

25

30

35

40

45

0 1 2 3

INTENSITY • 0=NONE0=NONE• 1=weak1=weak• 2=intermediate2=intermediate• 3=strong3=strong

%

Examples

Colour intensities Examiner 1

Examiner 2

1 2 3

1 33 6 0

2 14 54 11

3 0 12 45

Kappa beregning i Stata

• kap v1 v2, tab

• v2

• v1 1 2 3 Total•• 1 33 6 0 39 • 2 14 54 11 79 • 3 0 12 45 57 •• Total 47 72 56 175

• Expected• Agreement Agreement Kappa Std. Err. Z Prob>Z•• 75.43 34.98% 0.6221 0.0539 11.53 0.0000

Histological subtypesHistological subtypes IntensityIntensity

SubtypeSubtype11 22 33 TotalsTotals

Adenoid cystic Adenoid cystic

carcinomacarcinoma33 2323 2828 5454

MucoepidermoidMucoepidermoid

carcinomacarcinoma88 88 1515 3131

Acinic cellAcinic cell

carcinomacarcinoma77 1515 00 2222

Polymorph low Polymorph low grade adenoc.grade adenoc.

44 1212 55 2121

Adenocarcinoma Adenocarcinoma NOSNOS

44 44 22 1010

Squamous cellSquamous cell

carcinomacarcinoma33 44 00 77

Carcinoma ex. Carcinoma ex. pleomorphpleomorph

44 22 11 77

Overlevelsesanalyser

Follow-up tid: Tid fra diagnose (dato for den første gang patienten ses på en Øre-Næse-Hals afdeling i forbindelse med aktuelle cancerdiagnose) til censorering, som kunne være:

1. Død2. Sidste follow-up tjek (9. september 2008 Fpas)Hvis patienten var død, blev dødsårsag registreret som en

af to:1. Død af sin spytkirtelcancer eller af komplikationer til

behandling af samme2. Død af andre årsager

Datoer

• Før selve beregningerne påbegyndes regnes datoer i Excel om til Stata-datoer:

• generate double ddate=date(doedcen, "MDY", 2020)

• generate double start=date(datoafd, "MDY", 2020)

• generate fol=ddate-start

• generate folaar=fol/365.25

CS analyser

• stset folaar, failure(mors)

• stsum

• sts graph

• sts list

• sts graph, ci

• stsum, by(ostint)

• sts graph, by(ostint)

CS hele materialet0

.00

0.2

50

.50

0.7

51

.00

0 5 10 15 20analysis time

Kaplan-Meier survival estimate

CS hele mat. med CI

0.2

5.5

.75

1

0 5 10 15 20analysis time

95% CI Survivor function

Kaplan-Meier survival estimate

CS i.f.t. OPN-status0

.00

0.2

50

.50

0.7

51

.00

0 5 10 15 20analysis time

ostint = 1 ostint = 2ostint = 3

Kaplan-Meier survival estimates

DSS hele materialet0

.00

0.2

50

.50

0.7

51

.00

0 5 10 15 20analysis time

Kaplan-Meier survival estimate

DSS hele mat med CI

0.2

5.5

.75

1

0 5 10 15 20analysis time

95% CI Survivor function

Kaplan-Meier survival estimate

DSS i.f.t. opn-status0.

000.

250.

500.

751.

00

0 5 10 15 20analysis time

ostint = 1 ostint = 2ostint = 3

Kaplan-Meier survival estimates

Proportional hazards assumption

• xi: stcox i.ostint, tvc(ostint) texp(ln(_t))

• P=0,071

Cox-regression

• xi: stcox i.ostint

•• _t Haz. Ratio Std. Err. z P>z [95% Conf. Interval]•

• _Iostint_2 .6793372 .2538967 -1.03 0.301 .3265545 1.413237• _Iostint_3 .639291 .2613488 -1.09 0.274 .2868921 1.424553

•

ConclusionConclusion

• Salivary gland carcinomas express Salivary gland carcinomas express osteopontinosteopontin

• Level of osteopontin expression cannot be Level of osteopontin expression cannot be used as a diagnostic or prognostic markerused as a diagnostic or prognostic marker

• Osteopontin is a potential target for anti-Osteopontin is a potential target for anti-cancer therapycancer therapy