J Korean Med Sci.  2017 Oct;32(10):1595-1602. 10.3346/jkms.2017.32.10.1595.

Poorly Differentiated Clusters in Colorectal Adenocarcinomas Share Biological Similarities with Micropapillary Patterns as well as Tumor Buds

• Hong M
• Kim JW
• Shin MK
• Kim BC

• KMID: 2400430
• DOI: http://doi.org/10.3346/jkms.2017.32.10.1595

Abstract

In colorectal carcinoma, poorly differentiated clusters (PDCs) are a poor prognostic indicator and show morphological continuity and behavioral similarities to micropapillary patterns (MPPs) as well as tumor buds (TBs). Epithelial-mesenchymal transition (EMT) and inhibition of cancer-stromal interactions may contribute to the development of PDCs. To clarify the biological nature of PDCs, we examined immunohistochemical stainings for β-catenin, Ki-67, E-cadherin, epithelial cell adhesion molecule (EpCAM), MUC1, and epithelial membrane antigen (EMA), which are associated with EMT and cancer-stromal interactions. The expression frequencies and patterns of PDCs, TBs, and differentiated neoplastic glands from the tumor center (TC) were compared. In the study group (117 cases), the nuclear β-catenin staining index was higher in PDCs (37.3%) and TBs (43.3%) than in neoplastic glands from TC (8.9%, P < 0.001). The mean Ki-67 labeling index in TC was 71.5%, whereas it was decreased in PDCs (31.2%) and TBs (10.2%, P < 0.001). E-cadherin and EpCAM displayed a tendency to be found along the cell membrane in TC samples (91.5% and 92.3%, respectively), whereas they showed loss of membranous staining in PDC (44.4% and 36.8%, respectively) and TB samples (60.7% and 68.4%, respectively). An inside-out pattern for MUC1 and EMA was frequently observed in PDC (48.7% and 45.3%, respectively) and TB samples (46.2% and 45.3%, respectively), but not in TC samples. Our data demonstrate that there is a pathogenetic overlap among PDCs, TBs, and MPPs and suggest that they might represent sequential growth patterns that branch from common biological processes such as dedifferentiation and alteration in cancer-stromal interactions.

Keyword

Colorectal Carcinoma; Poorly Differentiated Clusters; Tumor Budding; Micropapillary

MeSH Terms

Adenocarcinoma*
Biological Processes
Cadherins
Cell Membrane
Colorectal Neoplasms
Epithelial Cells
Epithelial-Mesenchymal Transition
Mucin-1
Cadherins
Mucin-1

Figure

• 

  Fig. 1 Histopathological findings of PDCs. (A) PDCs in CRC are usually identified with TBs at the invasive front. (B) PDCs surrounded by clear, artifactual retraction spaces display a morphological overlap with micropapillary clusters (H & E staining; original magnification, × 200). PDC = poorly differentiated cluster, CRC = colorectal carcinoma, H & E = hematoxylin and eosin.

• 

  Fig. 2 Indices of nuclear β-catenin and Ki-67. (A) Indices of nuclear β-catenin are higher in PDCs and TBs than in differentiated glands in the TC. (B) Ki-67 labeling indices are higher in differentiated glands than in PDCs and TBs. PDC = poorly differentiated cluster, TB = tumor bud, TC = tumor center.

• 

  Fig. 3 Expression patterns of β-catenin, Ki-67, E-cadherin, EpCAM, MUC1, and EMA. (A) Nuclear β-catenin expression is more frequently identified in PDCs and TBs than in differentiated glands from the TC (inset). Differentiated glands show membranous β-catenin expression. (B) Ki-67 labeling indices are lower in the TBs and PDCs than in the differentiated glands (inset). (C) Membranous expression of E-cadherin is decreased in PDCs and TBs, whereas it is preserved in the differentiated glands. (D) Loss of EpCAM staining is observed in PDCs and TBs but not in the differentiated glands. (E) The I/O pattern of MUC1 is seen in the PDCs and TBs, while the apicoluminal pattern is observed in the neoplastic glands from the TC (inset). (F) The apicoluminal pattern is noted in the differentiated glands (inset), and the I/O pattern of EMA is observed in the PDCs and TBs (original magnification, × 200). EpCAM = epithelial cell adhesion molecule, EMA = epithelial membrane antigen, PDC = poorly differentiated cluster, TB = tumor bud, TC = tumor center, I/O = inside-out.

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