LncRNA HCG11 accelerates the progression of hepatocellular carcinoma via miR-26a-5p/ATG12 axis.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers globally. LncRNA HLA complex group 11 (HCG11) has been reported to play an oncogenic role in multiple cancers. Nevertheless, the role and regulatory mechanism of HCG11 in HCC are not fully addressed. PATIENTS AND METHODS: The abundance of HCG11 and miR-26a-5p was measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in HCC tissues and cells. Cell proliferation, apoptosis, metastasis, and autophagy were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell migration, invasion assays, and Western blot assay, respectively. The binding sites between miR-26a-5p and HCG11 or autophagy-related 12 (ATG12) were predicted by starBase bioinformatic software, and the combination was confirmed by Dual-Luciferase reporter assay. The abundance of ATG12 was examined by Western blot assay. Murine xenograft model was established to validate the function of HCG11 in vivo. RESULTS: The enrichment of HCG11 was enhanced in HCC tissues and cells and was negatively related to the prognosis of HCC patients. The abundance of miR-26a-5p was inversely correlated with the level of HCG11 in HCC tissues. HCG11 interference suppressed the proliferation, metastasis, and autophagy while promoted the apoptosis of HCC cells. MiR-26a-5p bound to lncRNA HCG11 and ATG12. The depletion of miR-26a-5p or the accumulation of ATG12 could alleviate the suppressive effects induced by HCG11 intervention on the proliferation, metastasis, autophagy, and the promoting impact on the apoptosis of HCC cells. HCG11 promoted the growth of murine xenograft tumor and autophagy through miR-26a-5p/ATG12 axis in vivo. CONCLUSIONS: LncRNA HCG11 accelerated the proliferation, metastasis, and autophagy while impeded the apoptosis of HCC cells via HCG11/miR-26a-5p/ATG12 axis. HCG11 might be a potential therapeutic target for the treatment of HCC.

[Application of recurrent neural network in prognosis of peritoneal dialysis].

OBJECTIVE: Deep learning models, including recurrent neural network (RNN) and gated recurrent unit (GRU), were used to construct the clinical prognostic prediction models for peritoneal dialysis (PD) patients based on routine clinical data. The performance of the RNN and GRU were compared with logistic regression (LR), which is commonly used in medical researches. The possible underlining clinical implications based on the result from the GRU model were also investigated. METHODS: We used the clinical data from the PD center of Peking University Third Hospital as the data source. Both the baseline data at the beginning of dialysis, and the follow-up and prognostic data of the patients were used by the RNN and GRU prediction models. The hyper-parameters were tuned based on the 10-fold cross-validation. The risk prediction performance of each model was evaluated via area under the receiver operation characteristic curve (AUROC), recall rate and F1-score on the testset. RESULTS: A total of 656 patients with the 261 occurrences of death were included in the experiment. The total number of all diagnostic records were 13 091. The results on the testset showed that the AUROC of the LR model, RNN model, and GRU model was 0.701 4, 0.786 0, and 0.814 7, respectively. The predictive performances of the GRU and RNN models were significantly better than that of the LR model. The performances of the GRU and RNN models assessed by recall rate and F1-score were also significantly better than that of the LR model, in which the GRU model reached the best performance. In addition, the recall rates were different among different causes of death or by different prediction time windows. CONCLUSION: The recurrent neural network model, especially the GRU model, is more effective in predicting PD patients' prognosis as compared with the LR model. This new model may be helpful for clinicians to provide timely intervention, thus improving the quality of care of PD.

[Mortality trend and age-period-cohort analysis of colorectal cancer among residents in Yangpu District of Shanghai from 1975 to 2014].

Objective: To describe the 40-years trend for the mortality of colorectal cancer (CRC) in Shanghai and to estimate the effect of age, period, and birth cohort with Age-Period-Cohort (APC) model. Methods: Data on tumor-releated death from 1975 Janurary 1 to 2014 December 31 was derived from the Yangpu District of Shanghai Center for Diseases Prevention and Control tumor registration system. Colonrectal cancer cases (C18.2-C18.9 and C20 in ICD10) were selected for analyses. Crude mortality, age-adjusted mortality, and Average Annual Percent Changes (AAPCs) were calculated for colon cancer and rectal cancer. The difference of AAPCs between male/female and different age groups were tested. An APC model (reference cohort and period were 1900 and 1975, respectively) was constructed to estimate the age-effect, period-effect, and cohort-effect on the colorectal cancer death. Results: During 1975-2014, 6 725 cases died of colorectal cancer (the cased of colon and rectal cancer were 3 684 and 3 041, respectively). The crude mortality and age-adjusted mortality of colon cancer was 8.83/100 000 and 6.76/100 000, respectively. The crude mortality and age-adjusted mortality of rectal cancer were 7.32/100 000 and 5.67/100 000, respectively. For population in Yangpu District, the crude mortality and age-adjusted mortality of colon cancer increased with time, and the crude mortality of rectal cancer increased with time (P<0.001). AAPC of the crude mortality rate (5.6%) and age-adjusted mortality rate (2.3%) of colon cancer were higher than those in rectal cancer (3.0% and -0.3%), respectively (both P values <0.001). AAPC of the crude mortality rate (males vs. females was 6.2% vs. 5.0%, P<0.05) and age-adjusted mortality rate (males vs. females was 2.7% vs. 1.7%, P<0.05) of colon cancer were higher in males than in females. APC model indicted that CRC-related death increased with age. During 1901 to 1941, the RR values of cohort effects for colon and rectal cancer death were 1.09-5.57 and from 1.04-2.28, respectively; During 1946 to 1991, the RR values of cohort effects for colon cancer and rectal cancer were 5.51-4.32 and 2.16-0.89. Conclusion: From 1975 to 2014, the mortality of CRC in Yangpu District increased gradually, and colon cancer mortality in males increased faster than that in females. The risk of death from colorectal cancer in the 1946-1991 birth cohort declined.

[Risk factors analysis and a new risk scoring system predicting hepatocarcinogenesis for chronic genotype C HBV infected patients].

Objective: To investigate the effects of hepatitis B virus (HBV) genotype and mutations on the development of hepatocellular carcinoma (HCC) and to establish a new qualified HCC risk scores. Methods: A cohort study enrolling patients with chronic HBV infection was conducted. HBV genotypes were identified by nested multiplex PCR. HBV mutations in the basic core promoter region and PreS region were sequenced after PCR amplification. Scores on risk factors were set based on nomogram. Results: Totally, 1 525 patients were followed-up in this research. A total of 1 110 patients infected with genotype C were followed-up for 8.52 (Q(R): 5.36-11.68) years on average, of whom the incidence of HCC was 11.93/1 000 person-years. In genotype C HBV infected patients, male gender, aged 40 years and over, and four DNA mutations (T1674CG, A1762T/G1764A, A3120T, and A2962G) can increase the risk of HCC (P<0.05); interferon therapy can reduce the risk of HCC (P<0.05). A new HCC predicting model was established according to the results. After validation, the predicted disease-free survival rate was consistent with the real one. Conclusions: Hepatitis B virus genotypes and mutations were closely associated with HCC. The new risk scoring system can well predict HCC occurrence in genotype C HBV infected patients.

[Epidemic characteristics and prophylaxis/control measures of infectious diseases caused by hydrological disasters].

Hydrological disasters are associated with infectious disease outbreaks and epidemics. Hydrological disasters will lead to water pollution, increased vulnerability to diseases, and increased density of vectors. These factors will facilitate the outbreaks of water-borne/food-borne diseases, vector-borne diseases, and air-borne/contagious diseases. Pre-event preparedness for disasters and post-event reconstruction of both disease surveillance system and water-supply system are key measures to prevent infectious disease outbreaks caused by hydrological disasters. This study reviews the domestic and overseas experiences of controlling infectious diseases after hydrologic disasters, outlines the spectrum of post-disaster infectious disease as well as their epidemiological characteristics, and provides practicable suggestions accordingly.

[Hepatocellular carcinoma: co - evolution of hepatocytes and hepatitis B virus].

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). In the process from chronic HBV infection to the development of HCC, there is a phenomenon of co-evolution of hepatocytes and HBV. The evolution of hepatocytes includes dedifferentiation and reverse evolution, while the evolution of HBV is mainly "telemorphosis" . Since HBV evolution occurs earlier than the development of HCC, the interaction between them is mainly reflected in the promotion of HCC evolution by HBV mutation. This article briefly summarizes the novel theory termed as cancer evolution and development and elucidates the molecular mechanism of HCC caused by HBV from the perspective of evolution.

Relationship between the angle of vertebral screws and spinal lateral angulation after fixation of thoracolumbar fractures via an anterior approach.

This study investigated possible contributors to lateral spinal angulation after surgical fixation of thoracolumbar fractures via an anterior approach. We retrospectively examined lateral angulation in 172 cases of thoracolumbar fractures treated in this manner. The coronal Cobb angle and angles of the screws relative to the endplates were determined from radiographs. The patients completed the Short Form 36, Oswestry Disability Index, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, and Visual Analogue Scale at the final follow-up visit. The mean coronal Cobb angle was 0.75° ± 3.91° (-14.25° to 14.55°) preoperatively, 3.17° ± 4.07° (-8.18° to 14.01°) immediately postoperatively, and 3.46° ± 4.21° (-1.05° to 17.27°) at the final follow-up visit. The superior posterior and inferior anterior screws were more parallel to their respective endplates when the approach was made ≥2 vs ≤1 vertebral levels above the fracture (P < 0.001). Lateral angulation was more likely when the approach was made ≤1 vs ≥2 levels above the fracture (P < 0.001). The coronal Cobb angle differed significantly (P < 0.01) between patients with lumbar and thoracic fractures. The immediate postoperative coronal Cobb angle correlated tightly with the sum of the screw angles (superior plus inferior posterior and/or inferior plus superior anterior). Lateral angulation may occur after surgical fixation of thoracic and lumbar fractures via an anterior approach. Non-parallelism between the vertebral screws and their corresponding endplates may predict postoperative lateral spinal angulation. Postoperative lateral angulation does not correlate with low back pain, quality of life, or preoperative lateral angulation.

Effect of bilateral deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease.

OBJECTIVE: A prospective cohort study to evaluate the efficacy of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on freezing of gait (FOG) in patients with advanced Parkinson's disease. METHODS: Patients (n = 10) with advanced Parkinson's disease were surgically implanted with microelectrodes to facilitate STN-DBS. Evaluations of FOG, motor function, activities of daily living and neuropsychological function were carried out in on-medication and off-medication states (with and without levodopa treatment), before surgery and at 6 and 12 months postoperatively. RESULTS: STN-DBS was associated with significant improvement in FOG score and neuropsychological function at both 6 and 12 months postoperatively, compared with preoperatively. Significant postoperative improvements were also observed in motor function and activities of daily living. Daily levodopa dosage was significantly lower at both 6 and 12 months postoperatively. CONCLUSIONS: STN-DBS improved FOG in patients with advanced Parkinson's disease. The significant reduction in levodopa dosage and improvement in neuropsychological function may be the reason for the therapeutic effect seen with STN-DBS.

Pioglitazone prevents smoking carcinogen-induced lung tumor development in mice.

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is known to have anti-tumor activity by inducing tumor cell apoptosis. However, it is unknown whether it can be used to prevent smoking carcinogen-induced lung tumor development. We induced mouse lung tumors using smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given at two early stages before the tumor formation. The role and the functional mechanism of PGZ were investigated in the development of mouse pulmonary tumors. The tumor development was monitored and PPARγ activity and endogenous PPARγ ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ before alveolar hyperplasia formation (Group NPa) and at the early phase of alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor development especially in Group NPb mice (all p < 0.05). PGZ not only prevented the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but also increased 13(S)-HODE level in Group NPb mice. PPARγ transcriptional activity was increased in NNKstimulated lung tissues when PGZ was given. The in vivo results were confirmed in the human lung cancer cells, which showed that PGZ induced lung cancer cell apoptosis through up-regulating nuclear PPARγ expression, inducing PPARγ transcriptional activity and increasing the levels of PPARγ ligands in NNK-treated cells. The early application of PGZ is able to prevent NNK-induced lung tumor development through maintaining the level of endogenous PPARγ ligands 15(S)-HETE and 13(S)-HODE and activation of PPARγ.

4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A2 and its receptor.

The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer is poorly understood. This study was conducted to study the role of TxA(2) in smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased TxA(2) synthase (TxAS) expression and thromboxane B(2) (TxB(2)) generation in cultured lung cancer cells, the result of which was supported by the increased level of TxAS in lung cancer tissues of smokers. Both TxAS-specific inhibitor furegrelate and TxA(2) receptor antagonist SQ29548 completely blocked NNK-mediated cell survival and growth via inducting apoptosis. TxA(2) receptor agonist U46619 reconstituted a near-full survival and growth response to NNK when TxAS was inhibited, affirming the role of TxA(2) receptor in NNK-mediated cell survival and growth. Suppression of cyclic adenosine monophosphate response element binding protein (CREB) activity by its small interference RNA blocked the effect of NNK. Phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) also had a positive role. Altogether, our results have revealed that NNK stimulates TxA(2) synthesis and activates its receptor in lung cancer cells. The increased TxA(2) may then activate CREB through PI3K/Akt and extracellular ERK pathways, thereby contributing to the NNK-promoted survival and growth of lung cancer cells.

Combined hepatocellular-cholangiocarcinoma: a clinicopathological study.

Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16-79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n = 18) of tumours were 'mixed' tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a 'fibrolamellar' tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin-producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin-negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum alpha-fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC-CC were short. In conclusion, HCC-CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.

Pre-operative chemotherapy for squamous cell carcinoma of the oesophagus: do histological assessment and p53 overexpression predict chemo-responsiveness?

Pre-operative chemotherapy is increasingly used in the treatment of oesophageal carcinoma. However, no features have been identified which can reliably predict a positive response to chemotherapy. The aim of this study was to examine whether histological features and p53 overexpression could predict such response. Prechemotherapy endoscopic biopsies from 55 patients, who subsequently completed two courses of chemotherapy followed by surgical resection, were studied. Patients were classified into responders and non-responders according to clinical and pathological findings. Pathological features of the endoscopic biopsies examined included adequacy of the tumour tissue, histological grade, degree of keratinisation, histologic patterns, mitotic rates and nuclear pleomorphism. Biopsy specimens were also tested for p53 overexpression using p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. Histologic features and p53 expression were correlated to chemoresponsiveness. 76% (42 of 55) of patients had sufficient biopsy tissue for assessment. Response to chemotherapy was evident in 64% (n = 27) of patients. None of the non-responders had tumours with high-grade nuclear pleomorphism compared with 37% (10 of 27) of responders (P = 0.01). All patients with high-grade nuclear pleomorphism responded to chemotherapy. No significant differences were found between the responders and non-responders with respect to tumour differentiation (P = 0.7), degree of keratinisation (P = 0.3) and mitotic rates (P = 0.8). Overall, p53 overexpression was noted in 67% (28 of 42) of patients. This was more prevalent in non-responders (12/15) compared to responders (16/27), but this was not statistically significant (P = 0.08). The degree of p53 overexpression had no significant relationship with responsiveness to chemotherapy. High-grade nuclear pleomorphism, identified on pretreatment biopsy specimens, correlated with response to chemotherapy, whereas p53 overexpression did not correlate with response. Improved tissue sampling and further investigations should be done so that the assessment of prechemotherapeutic endoscopic biopsies can have significant impact on clinical decision making.

Gastrointestinal autonomic nerve tumor of the esophagus. A clinicopathologic, immunohistochemical, ultrastructural study of a case and review of the literature.

BACKGROUND: Gastrointestinal autonomic nerve (GAN) tumor is a rare tumor that is supposed to originate from the enteric autonomic plexus. The tumor is a subgroup of the gastrointestinal stromal tumor that usually occurs in the stomach and small intestine. METHODS: An intramural tumor located in the upper third of the esophagus of a 62-year-old Chinese female is reported. The tumor was removed by a three-phased esophagogastrectomy because of its large size. The tumor measured 6.5 cm x 5 cm x 4 cm. Its tissues were sampled, examined by light microscopy, immunohistochemistry, and electron microscopy. RESULTS: The tumor was vaguely encapsulated but had foci of partial infiltration of the capsule. It was comprised of spindle cells with moderate nuclear pleomorphism. The mitotic count was less than 1 per 10 high-power field. The tumor stained positive for vimentin, neuron specific enolase (NSE), and S-100 protein, and was negative for cytokeratins, synaptophysin, chromogranin, neurofilaments, muscle markers, HMB45, and CD34. Ultrastructural study revealed that the tumor had cytoplasmic processes interdigitated in a complex fashion that were held together by primitive junctions but not invested in basal lamina. Many neurosecretory granules and neurotubules were also noted. The diagnosis was GAN tumor of the esophagus. From previous reports, 43 cases (25 males, 18 females) of GAN tumor of other locations have been documented. The tumors were located almost exclusively in the stomach and small intestine; rare cases arose primarily in the retroperitoneum and mesentery. Some of these GAN tumors were observed in patients with Carney's triad (three cases), neurofibromatosis (two cases), and adrenal ganglioneuroma (one case). It appears that the biologic behavior of GAN tumors is aggressive but there are too few reports on which to conclude anything about their prognosis. The tumors are usually large, with low mitotic rate, and are positive for NSE and negative for muscle markers. CONCLUSIONS: To the authors' knowledge, this is the first time that GAN is described in the esophagus. The diagnosis can be made only on the basis of characteristic ultrastructural features.

Double sarcomatoid carcinomas of the oesophagus.

Sarcomatoid carcinoma of the oesophagus is uncommon. A case of double sarcomatoid carcinomas was identified in the oesophagus of a 48-year-old man. This is the fourth case of multiple primary sarcomatoid carcinomas of the oesophagus and the first case with detailed pathological features presented. The clinicopathological features of multiple primary tumours and sarcomatoid carcinoma of the oesophagus are also reviewed.

Studies on the synthesis and biological activities of 4'-(R)-hydroxy-5'-(S)-hydroxymethyl-tetrahydrofuranyl purines and pyrimidines.

A series of 4'-(R)-hydroxy-5'-(S)-hydroxymethyl-tetrahydrofuranyl purines and pyrimidines were synthesized by the reaction of 3,4-epoxy-5-(S,trans)-dimethoxymethyl-tetrahydrofuran and nucleobases under the catalysis of potassium tert-butoxide and 18-crown-6. Compounds 6a, 6c and 7b have shown significant inhibition on the growth of HL-60 cells. The phosphotriester and phosphodiester of isonucleoside 8a-d were synthesized and cytotoxic activities were reported. The conformation of isonucleosides in solution was studied by 1H NMR.

Measurement of extent of spread of oesophageal squamous carcinoma by serial sectioning.

OBJECTIVES: (1) To examine the prevalence and extent of intramural metastasis in squamous cell carcinomas of the oesophagus so as to delineate the resection margins for these tumours; (2) to devise an appropriate method for measurement of these lesions which takes into account of the contraction of the specimens after resection. METHODS: Oesophagectomy specimens were prospectively collected from 96 patients (87 males, nine females) with primary oesophageal squamous cell carcinoma over a two year period. The sizes of the tumours were measured in situ, after resection and after application of muscle relaxant (to regain their in situ length). The specimens were then serially sectioned for histological examination. RESULTS: The sizes of the tumours measured after application of muscle relaxant roughly corresponded to those measured in situ. Intramural metastasis was observed in 26% of the cases. Sixty four per cent (16 cases) of these were on the oral side, 72% (18 cases) on the gastric side, and 25% (nine cases) on both sides of the tumours. The most distant extent of intramural metastasis from the primary tumour was from 0.5 cm to 7.7 cm (mean = 3.4 cm) on the oral side, and 0.5 to 9.5 cm (mean 4 cm) on the gastric aspect of the tumour. Intramural metastasis was seen only in patients in whom the primary cancer had deep muscle infiltration. Multiple neoplastic lesions could be detected in 33% of the patients. Both intramural metastasis and multiple neoplastic lesions were associated with extensive lymph node infiltration. However, they had different histological features and extent of infiltration. CONCLUSIONS: Intramural metastasis was frequently observed in oesophageal squamous cell carcinoma. This implies that excision with wide margins should be considered for local control of the disease.

Prognostic implication of proliferative markers MIB-1 and PC10 in esophageal squamous cell carcinoma.

BACKGROUND: Proliferative markers are related to tumor behavior. The commonly used markers are proliferating cell nuclear antigen (PCNA) and Ki-67. The aim of this study is to evaluate the usefulness of MIB-1 (for Ki-67) and PC10 (for PCNA) in the assessment of the clinicopathologic features and prognosis in patients with esophageal squamous cell carcinoma. METHODS: One hundred patients (88 males, 12 females; mean age, 63 years [range, 39 to 83 years]) with surgically resected esophageal squamous cell carcinoma (32 well differentiated, 51 moderately differentiated, and 17 poorly differentiated) were studied. The clinicopathologic features and survival data of these patients were noted. Representative tissue was collected from each tumor and immunohistochemical preparations for MIB-1 and PC10 were made. RESULTS: The percentages of cells that tested positive for PC10 and MIB-1 were much higher in tumor cells than in nonneoplastic cells. The pattern of expression of both markers varied with the differentiation of the tumor. The results observed with MIB-1 staining were better than those with PC10; because MIB-1 had less background staining, as well as stronger and more uniform positive signals compared with PC10. Thus, further investigation was performed on MIB-1-stained sections. The tumor cell MIB-1 scores ranged from 169 to 964 positive cells per 1000 cells (mean 598 +/- 211; median, 636). Although it was significantly associated with the differentiation of the tumor (P = 0.0001), the score had no significant relationship to the tumor size, location, or stage, or to the patients' age and sex. The prognosis depended on the size and stage of the lesion. In Stage III lesions (n = 83), patients with MIB-1 scores below 300 had longer actual survival rates than those with a score of 300 or above. However, the survival rates of patients in the latter group were better if the greatest dimension of the tumor diameter was 7.5 cm or less. CONCLUSIONS: Proliferative activity in esophageal squamous cell carcinoma, as defined by the MIB-1 immunohistochemical method, is significantly related to tumor differentiation. It is also potentially valuable as a prognostic marker in addition to its use in tumor staging and size.

Cytokeratin expression in non-neoplastic oesophageal epithelium and squamous cell carcinoma of the oesophagus.

The expression of cytokeratins (CK) 19, 8, 18, 13, 10 and 7 was examined in 35 cases of squamous cell carcinomas of the oesophagus (10 well-differentiated, 13 moderately-differentiated, and 12 poorly-differentiated) and the adjacent mucosa by means of a panel of monoclonal antibodies on frozen sections. The study was undertaken to assess the pattern of expression of these keratins in oesophageal tumours and its relation to the degree of differentiation. The normal oesophageal epithelia expressed CK19 in 86%, CK18 in 17% and CK13 in 14% of cases. CK8, CK10 and CK7 immunoreactivity was not observed. The tumours expressed CK19 in 86%, CK8 in 46%, CK18 in 97%, CK13 in 83%, CK10 in 34% and CK7 in 29% of cases. Thus, the so-called simple epithelial markers CK18 and CK19 occurred in the majority of oesophageal squamous cell carcinomas. CK13 (the so-called non-keratinizing squamous epithelial marker) was only infrequently demonstrated in the non-neoplastic oesophageal mucosa, and its expression was more frequent in carcinomas. CK10 was not demonstrated in non-neoplastic mucosa, but was mostly associated with well-differentiated carcinomas. We therefore conclude that the pattern of expression of cytokeratins in oesophageal carcinomas is different from that in normal oesophageal epithelia and varies with differentiation.