Poorly Differentiated Clusters Predict a Poor Prognosis for External Auditory Canal Carcinoma

Miyazaki, Masaru; Aoki, Mikiko; Okado, Yasuko; Koga, Kaori; Hamasaki, Makoto; Kiyomi, Fumiaki; Sakata, Toshifumi; Nakagawa, Takashi; Nabeshima, Kazuki

doi:10.1007/s12105-018-0939-x

Cited by 10 publications

(13 citation statements)

References 34 publications

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“…Three studies have evaluated the prognostic significance of PDC in other carcinoma types, including Crohn's disease-associated small bowel adenocarcinoma, [54][55][56] breast carcinoma and auditory canal carcinoma, with all finding high PDC grade to be significantly associated with adverse clinical outcomes. Interestingly, PDC grade in breast and auditory canal carcinomas was associated with strong interobserver agreement (kappa values 0.74 and 0.89, respectively), similar to that reported for CRC.…”

Section: Significance Of Pdc In Non-cr Cancersmentioning

confidence: 99%

Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice

et al. 2020

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Summary Poorly differentiated clusters (PDC), defined as small groups of ≥5 tumour cells without glandular differentiation, have gained recent attention as a promising prognostic factor in colorectal cancer (CRC). Numerous studies have shown PDC to be significantly associated with other adverse histopathological features and worse clinical outcomes. PDC may hold particular promise in stage II colon cancer, where risk stratification plays a critical role in patient selection for adjuvant chemotherapy. In addition, emerging evidence suggests that PDC can predict lymph node metastasis in endoscopically resected pT1 CRC, potentially helping the selection of patients for oncological resection. In ‘head‐to‐head’ comparisons, PDC grade has consistently outperformed conventional histological grading systems both in terms of risk stratification and reproducibility. With a number of large‐scale studies now available, this review evaluates the evidence regarding the prognostic significance of PDC, considers its relationship with other emerging invasive front prognostic markers (such as tumour budding and stroma type), assesses its ‘practice readiness’, addressing issues such as interobserver reproducibility, scoring methodologies and special histological subtypes (e.g. micropapillary and mucinous carcinoma), and draws attention to ongoing challenges and areas in need of further study. Finally, emerging data on the role of PDC in non‐colorectal cancers are briefly considered.

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Section: Significance Of Pdc In Non-cr Cancersmentioning

confidence: 99%

Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice

et al. 2020

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“…The biomolecular or prognostic factors associated with PDCs are similar to those of TB 38 . However, in a previous study we found that, even in cases with low‐grade TB, SCC‐EAC patients with high‐grade PDCs had a poor prognosis 6 . Thus, in this study, we selected both markers of invasive morphology, TB and PDCs (Figure ), for detailed investigation.…”

Section: Discussionmentioning

confidence: 90%

“…In SCC-EAC, cancer clusters surrounded by stroma and composed of 5 or more cancer cells were defined as PDCs. 6,24,25 To quantify PDCs, the whole tumor was first scanned under low magnification to identify the area with the most PDCs in CK immunostained sections. Next, the clusters within the microscopic field of a 20× objective lens (WHK 10× ocular lens; Olympus) were counted.…”

Section: Assessment Of Pdc Gradementioning

confidence: 99%

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Highly expressed tumoral emmprin and stromal CD73 predict a poor prognosis for external auditory canal carcinoma

et al. 2020

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Squamous cell carcinoma of the external auditory canal (SCC‐EAC) is rare and has a poor prognosis. The SCC‐EAC cases with high‐grade tumor budding (TB) or poorly differentiated clusters (PDCs) are associated with shorter survival than those with low‐grade TB or PDCs. Extracellular matrix metalloproteinase inducer (emmprin) is a protein expressed in tumor cells that stimulates the production of MMP‐2 by stromal fibroblasts to facilitate tumor invasion. Recently, we reported that emmprin forms a complex with CD73 to regulate MMP‐2 production from fibroblasts in vitro. Here, we examined the association of emmprin and CD73 expression with TB or PDCs as well as with survival in 34 biopsy specimens of SCC‐EAC patients. High tumoral emmprin expression was associated with highgrade TB, whereas high stromal CD73 expression was associated with high‐grade PDCs. Furthermore, concurrent elevated expression of tumoral emmprin and stromal CD73 was determined to be an independent poor prognostic factor. In immunoprecipitation analyses, complex formation between emmprin and CD73 was demonstrated in vitro. Production of MMP‐2 from fibroblasts was more abundant when cocultured with tumor cells than from fibroblasts cultured alone. Furthermore, MMP‐2 production was reduced by the transfection of CD73 siRNA in fibroblasts cocultured with tumor cells. The colocalization of emmprin and CD73 was enhanced in not only the peripheral cells of the tumor cell clusters that interact with fibroblasts but also in the cells of intratumor clusters. Overall, this study provides novel insights into the roles of emmprin, CD73, and MMP‐2 in tumor invasiveness.

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“…MPP should be distinguished from poorly differentiated clusters (PDCs) and tumour budding (36). MPP generally consists of 3-20 cells with cleft-like spaces and without fibrovascular cores at the interface with the stroma (6)(7)(8)(9)(10).…”

Section: Discussionmentioning

confidence: 99%

Villin is a biomarker for reverse polarity in colorectal micropapillary carcinoma

Zhao

Liu

et al. 2020

Oncol Lett

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Colorectal cancer (CRC) is a common malignant tumor of digestive system. CRC with micropapillary pattern (MPP) is an aggressive variant of colorectal adenocarcinoma. The aim of the present study was to clarify the clinicopathological significance and the prognostic role of an immunohistochemical marker, MPP, in CRC. The association between MPP and clinicopathological characteristics and prognosis in 286 cases of CRC (286/453 cases had follow-up information) were analysed. Then, 81 tissues without MPP and 90 tissues with MPP were analysed by immunohistochemistry using antibodies against villin, E-cadherin and epithelial membrane antigen (EMA). Bioinformatics was used to evaluate the expression of these three indicators in CRC. The proportion of micropapillary carcinoma in the overall tumour was ≥5%, and was observed in 90/453 cases (19.8%). The present data showed that CRC with MPP displayed higher rates of vascular and lymphatic invasion, a higher metastatic lymph node ratio and a higher pathological tumour and metastasis stage compared with CRC without MPP. The positive expression rates of EMA, E-cadherin and villin were 50.3, 93.4 and 96.5%, respectively. In 90 CRC cases with MPP, EMA inside-out pattern (I/OP) staining was observed in 26 cases (28.9%), and it was often focal and partial, while 37 cases (41.1%) had E-cadherin focal and partial staining compatible with reverse polarity. Villin I/OP staining was observed in 77 cases (85.6%), and circumferential staining predominated over partial staining. Overall, the data suggested that the presence of MPP is significantly associated with aggressive tumour behaviour and worse overall survival rate in CRC. Visualization and distinction of reverse polarity of colorectal micropapillary carcinomas is improved villin compared with EMA or E-cadherin.

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Poorly Differentiated Clusters Predict a Poor Prognosis for External Auditory Canal Carcinoma

Cited by 10 publications

References 34 publications

Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice

Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice

Highly expressed tumoral emmprin and stromal CD73 predict a poor prognosis for external auditory canal carcinoma

Villin is a biomarker for reverse polarity in colorectal micropapillary carcinoma

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