Invasive colorectal micropapillary carcinoma: an aggressive variant of adenocarcinoma

Kim, Mi Jung; Hong, Seung‐Mo; Jang, Se Jin; Yu, Eunsil; Kim, Jung Sun; Kim, Kyu Rae; Gong, Gyungyub; Ro, Jae Y.

doi:10.1016/j.humpath.2005.10.018

Cited by 93 publications

(80 citation statements)

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“…7 Several studies showed the prevalence of micropapillary carcinoma was 9-19% in colorectal carcinoma, and it was associated with aggressive histological features, including higher levels of lymphovascular invasion and perineural invasion, more frequent lymph node and distant metastases, and higher TNM stages (III/ IV). [8][9][10][11] In concordance with previous studies, we identified 10% of colorectal carcinoma with micropapillary carcinoma component from our cohort (55/561 cases), and micropapillary carcinoma was significantly associated with higher Figure 2 Kaplan-Meier survival analysis (log rank test). (a and b) Non-micropapillary carcinoma patients experience significantly better overall survival rates (Po0.0001, a) and disease-free survival rates (Po0.0001, b) than patients with micropapillary carcinoma.…”

Section: Discussionsupporting

confidence: 90%

“…Previous published studies found that the proportion of micropapillary carcinoma to the entire tumor ranged from 5 to 80%, and defined micropapillary carcinoma as carcinoma with at least 5% of micropapillary components. [8][9][10][11] On the other hand, as the identification of tumorinitiating cells, also referred to as cancer stem cells, in acute myeloid leukemia, their presence has also been identified in a number of solid tumor types, such as breast, lung, ovarian, brain, and colon cancer. [12][13][14][15][16][17] Emerging evidence suggests that stem cells have a crucial role not only in the embryonic development and maintenance of mature normal tissues, but also in the development of malignancies and disease progression associated with poor prognosis.…”

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Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

et al. 2013

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Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (Po0.0001) and lymph node metastasis (Po0.0001), higher pathological T and tumor node metastasis stages (P ¼ 0.047 and P ¼ 0.001), and more frequent SOX2 (P ¼ 0.038) and NOTCH3 expressions (P ¼ 0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, Po0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (Po0.0001) and multivariate (P ¼ 0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma. Modern Pathology (2013Pathology ( ) 26, 1123Pathology ( -1131 doi:10.1038/modpathol.2012 published online 12 October 2012 Keywords: colorectum; micropapillary carcinoma; prognosis; stem cell marker; TNM stage Colorectal cancer is one of the leading causes of cancer deaths worldwide, and both the prevalence and the incidence rate in South Korea are rapidly rising. 1 For metastatic colorectal cancer, the 5-year survival rate is only about 10%. 2 Micropapillary carcinoma is a relatively uncommon and distinctive tumor characterized by small clusters of tumor cells in the clear lacunar spaces, mimicking lymphatic or vascular channels. 3 Micropapillary carcinoma has high potential to metastasize to the regional l...

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Section: Discussionsupporting

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Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

et al. 2013

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“…Most cases were located in the sigmoid colon and the rectum. [8][9][10][11][12][13] Other studies have shown that micropapillary carcinoma is more commonly associated with lymphovascular invasion, lymph node metastasis and aggressive biological and clinical behavior. The inverted polarity of the cells that compose the micropapillary nests with an ''inside-out'' growth pattern, which has been shown by immunohistochemical and ultrastructural studies, 14,15 is probably related to its high invasive potential.…”

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Clinicopathological and molecular characterization of colorectal micropapillary carcinoma

Verdú¹,

Román²,

Calvo

et al. 2011

Modern Pathology

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Invasive micropapillary carcinoma is associated with frequent lymph node metastasis and adverse clinical outcome. Initially described as a variant of breast and ovarian carcinoma, it has subsequently been found in other organs, most recently the colon. Reports of colorectal micropapillary carcinoma to date are limited in number, and their molecular profile has not been established. The aims of the present study were to analyze their clinicopathological features and molecular profile, and compare them with those of conventional adenocarcinoma. Clinicopathological features of a cohort of 379 patients with primary colorectal cancer were retrospectively reviewed for the presence of the pattern characteristic of micropapillary carcinoma. We also assessed the expression of KRT7, KRT20, CEACAM5, MUC1 (EMA, clone E29), MUC1 (clone MA695), MLH1, MSH2, MSH6 and TP53 by immunohistochemistry. Genetic assessments of microsatellite instability, chromosomes 17p and 18q, and mutations in TP53, BRAF and KRAS were performed using DNA extracted from formalin-fixed, paraffin-embedded sections. In all, 60 of the reviewed cases (16%) had a micropapillary component that ranged from 5 to 95% of the tumor, characterized by a higher frequency of an infiltrative pattern, lymphovascular and perineural invasion, a higher depth of invasion and more positive lymph nodes than conventional adenocarcinoma. Immunohistochemistry for MUC1 (clone MA695) and MUC1 (EMA, clone E29) enhanced the characteristic inside-out staining pattern of the micropapillary carcinoma component, whereas the rest of the tumor showed luminal staining patterns. KRT7 expression was slightly increased in micropapillary carcinoma, but did not reach significance (17-3%, P ¼ 0.1967). The molecular parameters showed a higher frequency of TP53 alterations and a low incidence of microsatellite instability and RER phenotype (loss of mismatch repair protein) in micropapillary carcinoma. With regard to the histological parameters, micropapillary carcinoma appears to be more aggressive than conventional colorectal adenocarcinoma. The molecular profile supports the hypothesis that micropapillary carcinoma carcinogenesis develops through the classical chromosomal instability pathway.

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“…Except for the ovary, micropapillary carcinoma arising in many organs seems to pursue an aggressive clinical course because of frequent invasion into lymphatic spaces, metastasis into lymph nodes, or systemic metastasis (Verdú et al;Amin et al, 2002;Amin et al, 1994;Nassar;Nassar et al;Paterakos et al;Siriaunkgul & Tavassoli;Zekioglu et al;Haupt et al;Kim et al;Kuroda et al;Sakamoto et al;Wen et al;Xu et al). Micropapillary carcinoma of the colon macroscopically seems to be indistinguishable from conventional adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…The reported proportion of micropapillary carcinoma component to the entire tumor ranged from 5 to 80% and no pure cases has been reported. In gastrointestinal tract the most reported location is the sigmoid and rectum (Haupt et al, 2007;Kim et al, 2006;Kuroda et al, 2007;Sakamoto et al, 2005;Wen et al, 2008;Xu et al, 2009). In total, are near of 130 cases reported to date in colorectum.…”

Section: Introductionmentioning

confidence: 99%

Pure Micropapillary Rectal Carcinoma with CK7 and CK20 Coexpression and Loss of CDX2 Reactivity

Lino-Silva

2012

Int. J. Morphol.

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LINO-SILVA, L. S. Pure micropapillary rectal carcinoma with CK7 and CK20 coexpression and loss of CDX2 reactivity. Int. J. Morphol., 30(1):25-29, 2012. SUMMARY:The micropapillary carcinoma is regarded as an aggressive variant of adenocarcinoma in any location. Histologically is characterized by papillary cell clusters surrounded by clear spaces. The reported proportion of micropapillary carcinoma component to the entire tumor ranged from 5 to 80% and no pure cases has been reported. There are near of 130 cases reported to date in colorectum. We experienced a patient with a pure micropapillary carcinoma showing coexpression of CK7, CK20, and absence of CDX2, which had an aggressive neoplasm with extense perineural, vascular and lymphatic invasion also extensive nodal metastasis. The presence of a micropapillary carcinoma in the colorectum seemed to be closely related with nodal metastasis, similar to the case for micropapillary carcinomas in other organs. Therefore, if a micropapillary component is identified in a tumor, particularly in a biopsy specimen, even if the pre-operative diagnosis is a pedunculated early colorectal cancer, should be carefully consider the extent of surgical resection due to the high potential for nodal metastasis.

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Invasive colorectal micropapillary carcinoma: an aggressive variant of adenocarcinoma

Cited by 93 publications

References 19 publications

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells

Clinicopathological and molecular characterization of colorectal micropapillary carcinoma

Pure Micropapillary Rectal Carcinoma with CK7 and CK20 Coexpression and Loss of CDX2 Reactivity

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