PMID- 33177340
OWN - NLM
STAT- MEDLINE
DCOM- 20210129
LR  - 20230922
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 45
IP  - 1
DP  - 2021 Jan
TI  - Alterations in Ki67 Labeling Following Treatment of Poorly Differentiated 
      Neuroendocrine Carcinomas: A Potential Diagnostic Pitfall.
PG  - 25-34
LID - 10.1097/PAS.0000000000001602 [doi]
AB  - Assessment of the Ki67 index is critical for grading well-differentiated 
      neuroendocrine tumors (WD-NETs), which can show a broad range of labeling that 
      defines the WHO grade (G1-G3). Poorly differentiated neuroendocrine carcinomas 
      (PD-NECs) have a relatively high Ki67 index, >20% in all cases and commonly 
      exceeding 50%. After anecdotally observing PD-NECs with an unexpectedly low and 
      heterogeneous Ki67 index following chemotherapy in 5 cases, we identified 15 
      additional cases of treated high-grade neuroendocrine neoplasms (HG-NENs). The 
      study cohort comprised 20 cases; 11 PD-NECs, 8 mixed adenoneuroendocrine 
      carcinomas, and 1 WD-NET, G3 from various anatomic sites (gastrointestinal tract, 
      pancreas, larynx, lung, and breast). The Ki67 index was evaluated on pretreatment 
      (when available) and posttreatment samples. Topographic heterogeneity in the Ki67 
      index was expressed using a semi-quantitative score of 0 (no heterogeneity) to 5 
      (>80% difference between maximal Ki67 and minimal Ki67 indices). Relative to the 
      pretreatment group (n=9, mean Ki67 of 86.3%, range 80% to 100%), the neoplasms in 
      the posttreatment group (n=20, mean Ki67 of 47.7%, range 1% to 90%) showed a 
      significantly lower Ki67 index (18/20 cases). Of the 18 cases with a relatively 
      low Ki67 index, 15 showed heterogeneous labeling (mean heterogeneity score of 
      2.3, range 1 to 5) and in 3 cases it was a homogeneously low. This phenomenon was 
      observed in all subtypes of HG-NENs. In 6 cases, the alterations in Ki67 index 
      following treatment were sufficient to place these HG-NENs in the WHO G1 or G2 
      grade, erroneously suggesting a diagnosis of WD-NET, and in 9 cases there was 
      sufficient heterogeneity in the Ki67 index to suggest that a limited biopsy may 
      sample an area of low Ki67, even though hotspot regions with a Ki67 index of >20% 
      persisted. In 7 cases, the alterations in the Ki67 index were accompanied by 
      morphologic features resembling a WD-NET. These observations suggest that there 
      is a potential for misinterpretation of previously treated PD-NECs as WD-NETs, or 
      for assigning a lower grade in G3 WD-NETs. While the prognostic significance of 
      treatment-associated alterations in Ki67 index is unknown, awareness of this 
      phenomenon is important to avoid this diagnostic pitfall when evaluating treated 
      NENs.
FAU - Vyas, Monika
AU  - Vyas M
AD  - Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Tang, Laura H
AU  - Tang LH
FAU - Rekhtman, Natasha
AU  - Rekhtman N
FAU - Klimstra, David S
AU  - Klimstra DS
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (MKI67 protein, human)
SB  - IM
MH  - Antineoplastic Agents/therapeutic use
MH  - Biomarkers, Tumor/analysis
MH  - Carcinoma, Neuroendocrine/drug therapy/*pathology
MH  - Humans
MH  - Ki-67 Antigen/*analysis
MH  - Mitotic Index
MH  - Neoplasm Grading/*methods
PMC - PMC8549487
MID - NIHMS1631272
EDAT- 2020/11/13 06:00
MHDA- 2021/01/30 06:00
PMCR- 2022/01/01
CRDT- 2020/11/12 05:34
PHST- 2020/11/13 06:00 [pubmed]
PHST- 2021/01/30 06:00 [medline]
PHST- 2020/11/12 05:34 [entrez]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 00000478-202101000-00004 [pii]
AID - 10.1097/PAS.0000000000001602 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2021 Jan;45(1):25-34. doi: 10.1097/PAS.0000000000001602.