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Disclosure of Relevant Financial Relationships

USCAP requires that all faculty in a position to

influence or control the content of CME disclose any relevant financial

relationship WITH COMMERCIAL INTERESTS which they or their

spouse/partner have, or have had, within the past 12 months, which relates to

the content of this educational activity and creates a conflict of interest.

Dr. Stefano La Rosa declares he has no conflict(s) of interest to disclose

1996

2017

2000 2000 2004 2010

2006/2007

Grading

G1

G2

G3

Mitoses

m<2

2< m <20

m >20

Ki67 index

Ki67<2%

3%< Ki67<20%

Ki67 >20%

G1

G2

G3

Grading

G1

G2

G3

Mitoses

m<2

2< m <20

m >20

Ki67 index

Ki67<3%

3%< Ki67<20%

Ki67 >20%

G1

G2

G3

D. Klimstra

P. Komminoth

S. La Rosa

V. Adsay

G. Klöppel

2017

stomach

GEP system

Midgut-hindgut

GEP neuroendocrine neoplasms are a heterogeneous group of neoplastic proliferations characterized by specific clinico-pathological and molecular features which mainly depend on the site of origin

Stomach

La Rosa et al.,2011

G1-NET, rarely G3-NET

Take home message: Ki67 labeling index is a good prognostic marker but it should not be used alone to stratify patients in different prognostic categories; it should be considered together with clinico-pathologic tumor type and stage

Duodenum

• Ki-67: <2.5% (140 cases), 2.5-20% (31 cases)

• Mitoses: <2 (140 cases), 2-20 (16 cases)

• Grade: G1 (80%), G2 (20%)

• No WD-NET with Ki67>20%

• Morphology: well differentiated (176 cases)

Differences among NET subtypes

G1 G2

92% 8%

85% 15%

65% 35%

82% 18%

GP

Gatrinoma

D-cell tumor

NF- NET

Predictors of lymph node involvement

Proliferative grading, lymphovascular invasion and level of wall invasion can effectively predict LN metastases

Size, proliferative grade 2 and 3, lymphovascular invasion, wall invasion and stage III-IV are significantly related to worse survival.

Disease specific survival

Take home message:

•Ki67 labeling index is not useful to separate different tumor categories •Ki67 labeling index is a predictor of lymph node involvement •Although Ki67 labeling index is a predictor of disease free survival when considering duodenal NENs all together (G1, G2, G3), it does not discriminate alone the disease free survival between G1 and G2.

Upper jejunum

Lower jejunum and ileum (midgut)

Ki67<1% Ki67>1%

Take home message

Most ileal NETs are G1 and metastatic However: Ki67 is an independent predictor for tumor

progression 14% increased risk for tumor progression for each

increasing unit Ki67 is an independent risk factor for decreased

survival Ki67 cut-off at 5% seems better to discriminate

between G1 and G2

Appendix

Most tumors are G1 NETs, infiltrate

the muscular layer, but very rarely

metastasize

5HT S100

Take home message: For appendiceal NETs reporting tumor grade is

recommended by guidelines However, tumor grade is not statistically correlated with a

different survival, which mainly depends on stage

Rectum (hindgut)

Reference Jernman 2012 Hong 2013 Tsukamoto 2008 Kim 2013 Sohn 2015 Li 2015 Nakamura 2016

Total

72 37 23 79

972 147 170

1500

G1

61 33 17 79

906 137 166

1399 (93.2%)

G2

11 4 6 0

66 10 4

101 (6.8%)

Ki67 has been generally used for grading evaluation because

mitoses are extremely rare

Sohn et al. Cancer Res Treat 47:813, 2015

Sohn et al. Cancer Res Treat 47:813, 2015

Glicentin

L-cell NET EC-cell NET

Cut-off: 3%

Take home message: Most rectal NETs are G1 Ki67 index is a prognostic marker The recently proposed cut-off of 3% seems the best one Ki67 index should not be used alone as a prognosticator, but in association

with tumor size, lympho-vascular invasion, level of wall infiltration, and immunophenotype (L-cell versus EC-cell)

PRESENTATION TITLE

Important Information

Regarding CME/SAMs

The Online CME/Evaluations/SAMs claim process will only be

available on the USCAP website until September 30, 2017.

No claims can be processed after that date!

After September 30, 2017 you will NOT be able to obtain any

CME or SAMs credits for attending this meeting.

The value and pitfalls of Ki67 labeling index in gastrointestinal neuroendocrine

neoplasms

The value and pitfalls of Ki67 labeling index in gastrointestinal neuroendocrine

neoplasms

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