Hammam Olfat, Magdy Mona, Anas Amgad, Rahim Ali Abdel, Heedaya Mohamed, Helmy Ahmed
Department of Pathology Theodor Bilharz Research Institute (TBRI), Imbaba, Giza, Egypt.
Department of Hepato-gastroenterology, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza, Egypt.
Open Access Maced J Med Sci. 2017 Jul 31;5(5):595-602. doi: 10.3889/oamjms.2017.092. eCollection 2017 Aug 15.
HCC in Egypt usually occurs in HCV cirrhotic livers with poor prognosis due to late diagnosis. High hnRNPK & low Claudin-4 profiles indicate Epithelial Mesenchymal Transition (EMT), malignant transformation and high-grade tumours.
We studied the immunohistochemical expression of hnRNPK and Claudin-4 in HCV induced early HCC (eHCC) and adjacent liver tissue in Egyptian patients to improve eHCC detection in cirrhotic livers with better curative therapy options.
We studied the immunohistochemical expression of hnRNPK and Claudin-4 in 100 Egyptian patients resection specimens of HCV induced early HCC (eHCC) and adjacent liver tissue, in order to improve eHCC detection in cirrhotic livers, thus improving their therapeutic options.
Early HCC grade significantly directly correlated with nuclear hnRNPK/5HPFs count and inversely correlated with Claudin-4 expression %, with a converse correlation between hnRNPK and Claudin-4. Moreover in eHCC, combined hnRNPK ≥ 30/5HPFs & Claudin-4 ≥ 40% significantly distinguished low grade eHCC (G1) from high grade eHCC (G2&G3), with sensitivity 97% & specificity 69.7% for hnRNPK ≥ 30/5HPFs, and with sensitivity 70% & specificity 94.3% for Claudin-4 ≥ 40%. Moreover in the adjacent liver, both markers expressions significantly directly correlated with each other and with METAVIR fibrosis score but not with activity. Furthermore, 58% of eHCCs showed hnRNPK ≥ 30 Claudin-4 < 40% profile, indicating EMT type 3, compared to 26% with hnRNPK ≥ 30 Claudin-4 ≤ 10% profile in adjacent cirrhotic/ precirrhotic liver, with significant use of combined hnRNPK ≥ 30/5HPFs & Claudin 4 ≤ 10% as eHCC prediction cut offs in cirrhosis (p < 0.05).
Combination of hnRNPK and Claudin-4 can indicate early HCC development in HCV cirrhotic livers using hnRNPK ≥ 30/5HPFs & Claudin-4 ≤ 10% cut offs. Also, combination of hnRNPK ≥ 30/5HPFs & Claudin-4 ≥ 40% can distinguish low grade eHCC (G1) from high grade eHCC (G2&G3).
在埃及，肝癌通常发生于丙型肝炎病毒（HCV）所致的肝硬化肝脏中，由于诊断较晚，预后较差。高水平的不均一核糖核蛋白K（hnRNPK）和低水平的闭合蛋白-4（Claudin-4）表明上皮-间质转化（EMT）、恶性转化及高级别肿瘤。
我们研究了hnRNPK和Claudin-4在埃及患者HCV诱导的早期肝癌（eHCC）及相邻肝组织中的免疫组化表达情况，以改善在肝硬化肝脏中对eHCC的检测，并提供更好的治疗选择。
我们研究了100例埃及患者HCV诱导的早期肝癌（eHCC）切除标本及相邻肝组织中hnRNPK和Claudin-4的免疫组化表达，以改善对肝硬化肝脏中eHCC的检测，从而改善其治疗选择。
早期肝癌分级与细胞核hnRNPK/5个高倍视野（HPFs）计数呈显著正相关，与Claudin-4表达百分比呈负相关，hnRNPK与Claudin-4呈相反的相关性。此外，在eHCC中，联合检测hnRNPK≥30/5HPFs及Claudin-4≥40%可显著区分低级别eHCC（G1）与高级别eHCC（G2和G3），对于hnRNPK≥30/5HPFs，敏感性为97%，特异性为69.7%；对于Claudin-4≥40%，敏感性为70%，特异性为94.3%。此外，在相邻肝脏中，两种标志物的表达彼此之间以及与METAVIR纤维化评分均呈显著正相关，但与活动度无关。此外，58%的eHCC表现为hnRNPK≥30且Claudin-4<40%，表明为3型EMT，相比之下，在相邻的肝硬化/肝硬化前期肝脏中，26%的eHCC表现为hnRNPK≥30且Claudin-4≤10%，联合使用hnRNPK≥30/5HPFs及Claudin-4≤10%作为肝硬化中eHCC预测的截断值具有显著意义（p<0.05）。
联合检测hnRNPK和Claudin-4，采用hnRNPK≥30/5HPFs及Claudin-4≤10%的截断值，可提示HCV肝硬化肝脏中早期肝癌的发生。此外，联合检测hnRNPK≥30/5HPFs及Claudin-4≥40%可区分低级别eHCC（G1）与高级别eHCC（G2和G3）。
