Corrigendum: SPOCK1 promotes the development of hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.819883.].

SPOCK1 Promotes the Development of Hepatocellular Carcinoma.

The extracellular matrix proteoglycan SPOCK1 is increasingly recognized as a contributor to the development and progression of cancers. Here, we study how SPOCK1, which is present in non-tumorous hepatocytes at low concentrations, promotes the development and progression of malignant hepatocellular tumors. Although SPOCK1 is an extracellular matrix proteoglycan, its concentration increases in the cytoplasm of hepatocytes starting with very low expression in the normal cells and then appearing in much higher quantities in cells of cirrhotic human liver and hepatocellular carcinoma. This observation is similar to that observed after diethylnitrosamine induction of mouse hepatocarcinogenesis. Furthermore, syndecan-1, the major proteoglycan of the liver, and SPOCK1 are in inverse correlation in the course of these events. In hepatoma cell lines, the cytoplasmic SPOCK1 colocalized with mitochondrial markers, such as MitoTracker and TOMM20, a characteristic protein of the outer membrane of the mitochondrion and could be detected in the cell nucleus. SPOCK1 downregulation of hepatoma cell lines by siRNA inhibited cell proliferation, upregulated p21 and p27, and interfered with pAkt and CDK4 expression. A tyrosine kinase array revealed that inhibition of SPOCK1 in the liver cancer cells altered MAPK signaling and downregulated several members of the Sarc family, all related to the aggressivity of the hepatoma cell lines. These studies support the idea that SPOCK1 enhancement in the liver is an active contributor to human and rodent hepatocarcinogenesis and cancer progression. However, its mitochondrial localization raises the possibility that it has a currently unidentified physiological function in normal hepatocytes.

High early uterine vascular resistance values increase the risk of adverse pregnancy outcome independently from placental VEGF and VEGFR1 reactivities.

OBJECTIVE: From data in the literature, we hypothesized that high vascular resistance values in the uterine arteries at the end of the first trimester would increase adverse pregnancy outcomes and therefore might be accompanied by changes in VEGF/VEGFR1 immunoreactivities. STUDY DESIGN: In our university hospital 82 women (Study I n=62 and Study II n=20) were divided into two groups according to their uterine vascular resistance values. Uterine vascular resistance values were measured in the 10-13th weeks of gestation by color-Doppler ultrasonography. Women were divided into low and high vascular resistance groups. In the prospective follow-up study (Study I) the data of the pregnancy outcome were recorded. In cross-sectional study (Study II), VEGF and VEGFR1 immunoreactivities were measured on the tissue samples from women who underwent termination of pregnancy. RESULTS: In the high vascular resistance group (PI>2.3), the probability of adverse pregnancy outcome was significantly higher (40.0% vs. 12.8%). No differences in VEGF and VEGFR1 immunoreactivities were observed between groups. In both groups, intense VEGF immunoreactivity was observed in the maternal glandular epithelium and in the decidual cells. Weak reactivity was observed in the villous trophoblast. VEGFR1 immunoreactivity was intense in all regions. CONCLUSIONS: Our data suggest that high vascular resistance values in the first trimester are independent from VEGF/VEGFR1 immunoreactivities and markedly increase the probability of adverse pregnancy outcomes. This may be used for early screening of pregnant women in the first trimester.

Evaluation and comparison of the clinical, surgical and pathological TNM staging of colorectal cancer.

BACKGROUND/AIMS: The aim of our study was to compare the results of clinical, surgical and pathological staging of colorectal cancer. METHODOLOGY: 660 patients with colorectal carcinoma were included in the study. The results of the clinical, surgical and pathological staging were compared. RESULTS: Clinical T values were identical with the surgical in 75.15%, and with the pathological in 74.54% respectively. Surgical T values were identical with the clinical in 78.48%. In 67.27% of the cases the clinical evaluation of N value was identical with the surgical one. Clinical evaluation was identical with the pathological result in 60.60% of the cases. Surgical diagnosis of the lymph node metastasis matched the pathological finding in 76.66%. Regarding the M value, the coincidence of the diagnoses was as follows: clinical versus pathological 72.72%, surgical versus pathological 90.90%. Clinical and surgical TNM stages were by 79.09% in accordance. By decision of total TNM stage the clinical-pathological staging showed worse (76.06%), while surgical-pathological showed significantly better (88.48%) matching. CONCLUSIONS: Based on our results we can state that in a quarter of all colorectal cancer cases the extent of the primary tumor could not have been established correctly. The lymph node involvement was well defined in just over half of the cases only. The M values were accurately stated in about three quarters of the cases. High grade of conformity of clinical, surgical and pathological staging can result in better treatment-planning, short- and long-term survival, and higher quality of life.

Location and age at onset of colorectal cancer in Hungarian patients between 1993 and 2004. The high number of advanced cases supports the need for a colorectal cancer screening program in Hungary.

BACKGROUND: In recent decades, the incidence of proximal colorectal cancer (CRC) in North America and Western Europe has steadily increased, while that of the distal tumors has shown a corresponding decrease. Our aim was to investigate the change in age at diagnosis, the gender, location and cancer stage of CRC cases over the last 12 years in a large number of Hungarian patients. PATIENTS AND METHODS: The clinical and histological data of 1694 CRC patients (M/F: 917/777, age at diagnosis: 65.2 +/- SD 12.5 years), diagnosed at the First Department of Medicine and the First Department of Surgery of Semmelweis University, Budapest, Hungary, between January 1, 1993 and December 31, 2004, were analyzed retrospectively. RESULTS: CRCs were rectal or left-sided in 70% and proximal (transverse, ascending or cecum) in 30% of the cases. The proportion of rectal carcinomas increased over the observed period (1993-1998: 31.6% vs. 1999-2004: 42.1%, p=0.001), while the proportion of proximal tumors remained stable. Eleven percent of CRCs were diagnosed under the age of 50 years. The age at diagnosis did not differ between males and females, but was lower in patients with rectal tumors compared to other localizations (p=0.02); 75.7% of the CRCs were T3-T4 at diagnosis and lymph node metastases could be detected in 47.7%. CONCLUSION: In contrast to Western European and North American trends, the proportion of proximal CRCs did not increase in Hungary over the observed period. Almost two-thirds of all cancers were left-sided. The high percentage of locally advanced tumors and lymph node metastases supports the need for colorectal screening programs.

[Change in location of colorectal cancer in Hungarian patients between 1993-2004]. / A colorectalis rákok lokalizációjának változása Magyarországon 1993 és 2004 között.

UNLABELLED: The incidence of proximal tumours in Western countries has steadily increased while that of distal tumours has shown a corresponding decrease. Our aim was to investigate the prevalence, location and histology of colorectal cancers in the last twelve years in Hungarian patients. PATIENTS AND METHODS: Clinical data of 1738 patients diagnosed with colorectal tumors (M/F: 940/798, mean age at diagnosis: 65.2 +/- 12.5 years) between 1st of January 1993 and 31st of December 2004 at the 1st Internal Medicine and 1st Surgery Department of Semmelweis University were enrolled. Pathology and clinical data were analysed retrospectively. The observed periods were the following 1993-1998 and 1999-2004. RESULTS: 1694 (97.5%) of the patients had adenocarcinoma (CRC), 15 anaplastic cancers, 9 carcinoid, 6 planocellular, 5 GIST, 3 leiomyoma and 2-2 melanoma, lymphoma and shigillocellular cancers were diagnosed. 75.7% (943/1246) of the CRCs were diagnosed at locally advanced stage (T3-T4), and 47.7% (521/1093) of CRC patients had lymph node metastasis at the time of diagnosis. 11.0% of the CRCs were diagnosed in <50 year-olds (<40 years: 2.5%, <30 years: 0.5%). The location of the CRC was distal in 1186 (rectum: 53.9%, sigmoid/descending: 46.1) and proximal in 508 cases. Synchronous cancers were detected in 12 patients (age: 68.8 +/- 11.6 years, gender: 11 male/1 female, location: rectum and transverse in 6, rectum and ascending/caecum in 5 patients). Age at diagnosis was not different according to gender (M/F: 64.8 +/- 12.0 years vs. 65.8 +/- 12.9 years), but it was lower in patients with rectal cancer compared to left or right sided cancers (64.1 years vs. left: 66.1 years, right: 66.0 years, p = 0.02). Rectal CRC was more common in males, while the proportion of proximal cancers was lower (rectum, M/F: 41.2% vs. 33.5%, proximal M/F: 26.8% vs. 33.8%, p = 0.003). The proportion of rectal cancers increased over the observed period (1993-1998: rectal: 31.6% vs. 1999-2004: 42.1%, p = 0.002). CONCLUSIONS: In contrast to Western countries, the proportion of proximal CRC did not become higher in Hungary. Still more than two-third of the patients were diagnosed to have distal cancers. The proportion of male patients was higher in this subset of CRC. The high percentage of locally advanced and metastatic cancers supports the need for colorectal screening program in Hungary.

[Incidence and pathologic distribution of esophageal cancers at the gastro-esophageal junction between 1993-2003]. / A nyelocso és a gastrooesophagealis junctio daganatainak gyakorisága és szövettani megoszlása 1993-2003 között.

UNLABELLED: There was a significant change in the histology of oesophageal cancers in the last few decades. The incidence of oesophageal adenocarcinoma has risen considerably, now it is equally or even more prevalent than squamous cell cancers in some North American and Western European countries. As no Hungarian data is available, the authors' aim was to investigate the prevalence and histology of oesophageal and gastrooesophageal junction cancers in the last decade. PATIENTS AND METHODS: 451 patients diagnosed with oesophageal (n = 371, 296 male/75 female, mean age at diagnosis: 57.9 SD 10.1 years) or cardia (n = 80, 58 male/22 female, mean age at diagnosis: 65.2 SD 13.4 years) cancer between 1st of January 1993 and 31st of December 2003 at the 1st Internal Medicine and 1st Surgery Department of Semmelweis University were enrolled. Pathology and clinical data were analysed retrospectively. RESULTS: 93% (n = 345) of the patients with oesophageal cancer had squamous cell carcinomas, while adenocarcinoma was only diagnosed in 15 (4%) patients. Mean age at diagnosis was lower in patients with squamous cell cancer (57.4 SD 10.0 years) compared to patients with adenocarcinoma (66.9 SD 8.8 years, p = 0.001). Male-to-female ratio was 4:1 in patients with squamous cell carcinoma (277/68) and undifferentiated carcinoma (9/2), while it was 2:1 in patients with adenocarcinoma (10/5). According to the location 1.3% of cancers of the midthoracic oesophagus and 8.6% of the lower oesophagus were adenocarcinoma. The proportion of adenocarcinoma remained stable over the observed period (1993-1997: 3.7% vs. 1998-2003: 4.3%). In contrast, 71.25% (57/80) of the gastrooesophageal junction cancers and overall 15.9% (72/451) of the cancers of the oesophagus and gastrooesophageal junction were adenocarcinoma (1993-1997: 17.2% vs. 1998-2003: 14.7%). CONCLUSIONS: Since only a few percentages of authors patients with oesophageal cancers were diagnosed to have adenocarcinoma and its proportion remained stable over the observed period, it seems that in contrast to North American and Western European countries, adenocarcinoma is still infrequent in Hungary.