**6. Biopsy in the differential diagnostics of liver lesions**

**MicroRNA Change in the target tissue**

178 Recent Advances in Liver Diseases and Surgery

miR-150; miR-125b-2; miR-1179; miR139-3p

miR-93; miR-548e; miR-19b; miR-96; miR-548c-5p; miR-140-5p; miR-19a; miR-17-5p:9.1; miR-101; miR-579; miR-18b; miR-18a; miR-455-5p; miR-549; miR-219-5p; miR-33b; miR-330-5p; miR-301a

miR-196a-5p; miR-200b-3p;

miR-UL70-3p; miR-154-5p; miR-221-3p; miR-301b; miR-320b; miR-371a-5p; miR-486-5p; miR-572; miR-654-3p; miR-923

miR-21; miR-31; miR-93;

References: [12, 64–69].

**Table 4.** MiRNAs in colorectal cancer1

miR-103

1

miR-223-3p

**compared to the control**

miR-143 Decrease Liver metastasis of colorectal

miR-21 No difference Liver metastasis of colorectal

miR-143 Decrease Liver metastasis of colorectal

miR-29c Decrease Colorectal cancer with liver

miR-29c Increase Liver metastasis of colorectal

miR-21; miR-31; miR-93 Increase Liver metastasis of colorectal

miR-181a Increase Colorectal cancer with liver

miR-566 Decrease Colorectal cancer Normal tissues

miR-21 Increase Lymph node metastasis Normal tissues

cancer

cancer

cancer

metastasis

metastasis

metastasis

metastasis

metastasis

Increase Colorectal cancer Normal tissues

cancer

cancer

metastasis

Prognostic value has been reported regarding has been reported. In colorectal cancer, shorter disease-free interval was found in patients who exhibited higher miR-21 and higher miR-143

Increase Colorectal cancer with liver

Decrease Colorectal cancer with liver

Decrease Colorectal cancer with liver

Increase Colorectal cancer with liver

**Target tissue or body liquid Control tissues or body**

**liquid**

Normal colonic tissue

Colorectal cancer

Colorectal cancer

Colorectal cancer without distant metastasis

Colorectal cancer without distant metastasis

Colorectal cancer without distant metastasis

Colorectal cancer without distant metastasis

Colorectal cancer without distant metastasis

Colorectal cancer

Normal tissues

liver metastasis

Colorectal cancer without

Biopsy evaluation can yield reliable diagnosis of colorectal cancer. The tubular and cribrous glandular architecture in combination with high cylindrical neoplastic cells frequently is straightforward (Figure 1). Upon necessity, immunohistochemical evaluation can be applied as colorectal cancer is characterised by specific markers. Thus, the cytoplasmic expression of cytokeratin 20 (Figure 2) and nuclear presence of CDX2 protein (Figure 3) is virtually diagnostic of colorectal cancer.

**Figure 1.** Metastasis of colorectal cancer in liver tissue. Haematoxylin–eosin, original magnification 50×.

**Figure 2.** Intense cytoplasmic expression of cytokeratin 20 in colorectal cancer. Note the heterogeneity. Immunoperoxi‐ dase, anti-cytokeratin 20, original magnification 50×.

**Figure 3.** Diffuse intense nuclear expression of CDX2 in colorectal cancer. Immunoperoxidase, anti-CDX2, original magnification 100×.

In contrast to many other metastatic carcinomas, colorectal cancer lacks cytokeratin 7. Meta‐ static neuroendocrine tumours (Figures 4 and 5) can be excluded by the absence of chromog‐ ranin A, synaptophysin and CD56. The combination of several neuroendocrine markers is advisable, especially in a patient with clinically and/or endoscopically identified colorectal tumour, due to differential expression of these markers by gut origin (foregut *versus* midgut *versus* hindgut). The clinical relevance of correct differential diagnosis between metastatic colorectal adenocarcinoma and neuroendocrine tumours is high.

**Figure 4.** Metastasis of neuroendocrine carcinoma in the liver tissue. Haematoxylin–eosin, original magnification 50×.

**Figure 2.** Intense cytoplasmic expression of cytokeratin 20 in colorectal cancer. Note the heterogeneity. Immunoperoxi‐

**Figure 3.** Diffuse intense nuclear expression of CDX2 in colorectal cancer. Immunoperoxidase, anti-CDX2, original

In contrast to many other metastatic carcinomas, colorectal cancer lacks cytokeratin 7. Meta‐ static neuroendocrine tumours (Figures 4 and 5) can be excluded by the absence of chromog‐ ranin A, synaptophysin and CD56. The combination of several neuroendocrine markers is advisable, especially in a patient with clinically and/or endoscopically identified colorectal tumour, due to differential expression of these markers by gut origin (foregut *versus* midgut *versus* hindgut). The clinical relevance of correct differential diagnosis between metastatic

colorectal adenocarcinoma and neuroendocrine tumours is high.

dase, anti-cytokeratin 20, original magnification 50×.

180 Recent Advances in Liver Diseases and Surgery

magnification 100×.

**Figure 5.** Metastasis of neuroendocrine carcinoma in the liver tissue. Immunoperoxidase, anti-chromogranin A, origi‐ nal magnification 50×.

In contrast to hepatocellular carcinoma, colorectal cancer lacks hepatocyte antigen, glypican and cytoplasmic TTF-1 expression. Alpha-fetoprotein is absent from colorectal cancer tissues, although the differential diagnostic value is lower because of relatively infrequent expression in hepatocellular carcinoma. CD10 can be misleading in the differential diagnosis of hepato‐ cellular and metastatic colorectal cancer. Hepatocellular cancer mostly develops in the background of liver cirrhosis while metastases are rare in cirrhotic liver. However, hepatocel‐ lular carcinoma, and especially fibrolamellar variant, can arise in the absence of cirrhosis. In contrast, colorectal cancer metastasis can be surrounded by liver tissue that is damaged by peritumoural or treatment-related cell damage, fibrosis and inflammation [71].

The tissue analysis of cardinal tumour features and cancer microenvironment, production of cytokinesand growth factors in the metastasis, evaluation of circulating neoplastic cells, analysis of tumour hypoxia and angiogenesis atprotein, gene and miRNA levels can also bring prognostic and predictive information [72–77]. Besides the tumour characteristics, hepatic lymphatic anatomy and its involvement by tumour can be evaluated to predict the recurrence [15].
