Maarten van der Doelen

Chapter 2

IHC

NGS

DDR Other

Patient ID 01 B

Tissue origin PSMA AR 100

CD56 antigen 7

Chromogranin

Synaptophysin Ki67

BRCA1 AR

PPP2R2A PTEN

RB1

TP53

TMB (Muts/Mb)

02 03 04 05 06 07 08 09 10 11 12 13

P P L P P L L L B B L L

1

100

3

100

2

80

20

100

1

2

90

10

4,1

100

3

1,4

70

02 06 10 After Prior to 225 Ac-PSMA therapy B B B

30

1,9

100

4,5

2,2

100

100

15

2,6

7,5

3,2

100

15

2,2

100

0

5 Mb

x

x

x

80

4,1

100

2,1

15

2

100

0

5 Mb

Tissue origin

Gene alterations

B Bone

Not determined

L Lymph node

No alteration

P Prostate

Nonsense mutation Missense mutation Frameshift mutation Splice site mutation CNV - amplification

PSMA expression

Not evaluable H-score <200 H-score ≥200

CNV - deletion

AR expression

Not evaluable Low (<50%) Moderate (50-90%) Strong (≥90%)

NE marker expression Not evaluable Negative (<30%) Positive (30%-50%)

Strong positive (≥50%)

Ki-67 expression Not evaluable

Negative (<5%) Positive (5-20%) Strong positive (≥20%)

Figure 5. Immunohistochemical analyses and genomic profiling of patients with metastatic castration resistant prostate cancer prior and after treatment with 225 Ac-PSMA-617 targeted alpha-radiation therapy. AR, androgen receptor; DDR, DNA damage repair; IHC, Immunohistochemistry; NE, neuroendocrine; NGS, next generation sequencing; PSMA, prostate-specific membrane antigen; TMB, tumor mutational burden (mutations per megabase).

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