Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen,CD10, and alpha-fetoprotein

Hepatocyte monoclonal antibody (Hep) (alternatively Hep Par 1 for Hep paraffin 1) has been reported to stain normal hepatic tissue and hepatocellular carcinoma (HCC) with high specificity. We have studied the Hepatocyte expression in 96 cases of HCC and 311 cases of nonhepatic epithelial tumors. All cases of HCC were also stained with CEA-Gold 5, CD10, and alpha-fetoprotein. Hep, CEA-Gold 5, CD10, and alpha-fetoprotein immunostains were performed on formalin-fixed, paraffin-embedded tissue sections. Hep immunoreactivity was detected in 88 of 96 cases of HCC (92%), with a cytoplasmic and granular pattern of staining. The level of Hep expression in HCC corresponded to the nuclear grade and growth pattern. All 50 cases of nuclear grade 1 and nuclear grade 2 HCC were positive (100%), whereas 37 of 44 nuclear grade 3 (84%) and 1 of 2 nuclear grade 4 (50%) were positive. Sixty-seven of 68 cases of HCC with a trabecular, pseudoglandular, or scirrhous growth pattern were positive (98%), whereas 22 of 27 cases of HCC with a compact growth pattern were positive (81%). CEA-Gold 5, CD10, and alpha-fetoprotein immunoreactivity was detected in 76% (73 of 96), 52% (50 of 96), and 31% (30 of 96) cases of HCC, respectively. The positive predictive value of the combination of all four antibodies was 97%. Three cases of HCC were negative for all four antibodies; these cases had a high nuclear grade or a sarcomatoid or compact growth pattern. Twenty of 311 cases of nonhepatic tumors were positive for Hep (6%): 15 were adenocarcinomas and five were neuroendocrine tumors. The negative predictive value of Hep in HCC was 94%. The Hep-positive nonhepatic epithelial tumors were easily distinguished from HCC by the expression of keratin 7 or keratin 20 for adenocarcinoma and chromogranin and synaptophysin for neuroendocrine tumors because HCC does usually not express these markers. With the exception of two cases of hepatoid gastric carcinoma, all Hep-positive nonhepatic epithelial tumors were negative for alpha-fetoprotein, CEA-Gold 5, and CD10. Our study demonstrates that Hep is a relatively specific marker for HCC. It is useful in differentiating HCC from primary hepatic cholangiocarcinoma and metastatic tumors when combined with other immunomarkers.     

Prostate-specific antigen as a marker of adenocarcinoma of prostate

Summary Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels were measured in 117 patients with prostatic adenocarcinoma, in 9 patients with prostatic hyperplasia and in 14 patients with other malignancies to compare the clinical usefulness of the PSA and PAP levels. PSA was elevated (PSA⁺) in 14 of 18 untreated patients (78%) with prostatic cancer. PAP was elevated (PAP⁺) only in 3 of these untreated cases (17%). Also in previously treated patients PSA was more often positive than PAP. PSA was positive in 40 of the 99 treated patients (40%), PAP was elevated only in 21 cases (21%). There was a significantly (P<0.001) higher tendency towards elevated PSA in the prostatic cancer patients: 32 (27%) patients with PSA⁺ and PAP^- compared with only 2 cases (2%) with PAP⁺ and PSA^-. The PSA⁺/PAP^- patients were analyzed further. In seven of them the PSA level also returned to its normal level after orchiectomy or/and radiotherapy. In two patients the PSA levels indicated tumor progression earlier than PAP, their PAP levels did not rise until bone metastasizing was evident. There were also progressive disease in some patients evidenced only by increased PSA levels. In addition to cancer patients the PSA level was increased in three (30%) of the prostatic hyperplasia patients. It was also elevated in three patients with other malignancies. However, these three patients also had prostatic hyperplasia and the increase in the PSA level is considered more likely to be due to that. According to these findings it is suggested that PSA is more sensitive than PAP in local and advanced prostatic cancer and may be more useful in monitoring responses and recurrence after therapy.     

Clinical evaluation of a prostate-specific antigen as a serum marker of prostatic cancer

Combined measurement of serum prostate-specific antigen (PA) and prostatic acid phosphatase (PAP) was performed in 235 patients with various urologic diseases including 55 patients with prostatic cancer. A PA level of over 24.7 ng/ml and a PAP level of over 3.1 ng/ml were considered to be positive. The positive rate of PA was 57% in the patients with untreated prostatic cancer and 3% in the patients without prostatic cancer. The positive rate of PAP was 52% in the patients with untreated prostatic cancer and 1% in the patients without prostatic cancer. PA and PAP were considered to be equally sensitive and specific serum markers of prostatic cancer. However, the positive rate increased to 65% without increasing the false positive rate when the PA and PAP were both measured simultaneously. The combined assay of PA and PAP is recommended for screening prostatic cancer. The cross-over titer of PA and gamma-Sm using standard samples in each kit revealed linearity, which suggested that PA and gamma-Sm possess the same antigenicity.     

Prostate-specific antigen doubling time as a prognostic marker in prostate cancer

Prostate cancer has a varied natural history. Men with similar serum prostate-specific antigen (PSA) levels, clinical stages, and histologic features in their tissue specimens can have markedly different outcomes. While prostate cancer is lethal in some patients, most men die with cancer rather than because of it. Moreover, histologically apparent cancer can be found in the prostate glands of approximately 42% of men over 50 years of age who die from other causes, but the lifetime risk that a man in the US will be diagnosed with prostate cancer is estimated to be 11% and the risk of dying from the disease is only 3.1%. Consequently, appropriate disease management requires risk assessment. How likely is it that a given man's cancer will progress or metastasize over his remaining lifetime? What is the probability of successful treatment? What are the risks of adverse effects and complications of each treatment? Physicians use a variety of clinical and pathologic parameters to assess the risk that a given cancer poses to an individual patient. In addition to the accepted parameters of serum PSA level, clinical staging, and pathologic grading and staging, PSA doubling time has emerged as an important factor in the evaluation of men with newly diagnosed prostate cancer or prostate cancer that recurs after treatment. PSA doubling time can also be used as a surrogate marker for prostate cancer-specific death. This review summarizes current knowledge regarding the role of PSA doubling time as a prognostic marker in men with prostate cancer.     

Efficacy and discriminative ability of prostate-specific antigen as a tumor marker.

A study was performed on 175 men to compare the level of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (n = 83) and prostatic carcinoma (n = 92). There was a good correlation between T stage and increasing values of PSA. Using 2.5 ng/ml as the upper normal limit of PSA, the test sensitivity of PSA was 94%, but the specificity only 44%. Receiver-operator characteristic curve (ROC) analysis demonstrates that PSA is superior to prostatic acid phosphatase (PAP); this is particularly true in the higher T stages. Although ROC analysis shows that PSA is more discriminating than PAP, the sensitivity of PSA is dependent upon the choice of an appropriate cut-off point of the test. It was shown that PSA is not sufficient for detecting the presence or absence of prostatic cancer in a general population. However, PSA is the most sensitive marker in the detection of prostatic cancer.     

肠型脂肪酸结合蛋白对肠缺血早期诊断的意义

目的　探讨肠型脂肪酸结合蛋白 (IFABP)对肠缺血早期诊断的意义。方法　将SD大鼠随机分成对照组和肠系膜上动脉结扎组 (SMA组 ) ,分别于术前及术后 1,2 ,4h取血 ,检测各时点的血清IFABP、肌酸激酶 (CK )、肌酸激酶BB型同工酶 (CK BB)和乳酸脱氢酶 (LDH )。结果　对照组血清I FABP水平在各时点均无明显差异 (P >0 .0 5 )。SMA组结扎后 1h血清IFABP水平迅速增加 ,与对照组相比 ,差异具显著性 (P <0 .0 1) ;结扎 2h达高峰。血清中CK ,CK BB和LDH活性均随缺血时间的延长而出现升高趋势。与对照组相比 ,各组CK ,CK BB和LDH出现显著性升高的时间依次为缺血后1,2 ,4h(P <0 .0 5 )。结论　IFABP是小肠缺血性疾病的早期、特异、敏感的生化诊断指标。     

Gastric carcinoma: intestinal metaplasia and tumor growth patterns as indicators of prognosis

We have reviewed 200 cases of gastric carcinoma treated between 1970 and 1980 to assess the value of intestinal metaplasia in the stomach and tumor growth patterns in determining prognosis. Intestinal metaplasia was found to be more frequently associated with early gastric tumors, expanding-type tumors, and tumors located in the antrum. The survival rate was 53% with intestinal metaplasia and 34% without. Sixty-three percent of expanding tumors with metaplasia survived. If the lymph nodes were not involved, the survival rate with metaplasia was 81%. We conclude that intestinal metaplasia and growth patterns are valuable in predicting outcome. Preoperative evaluation of gastric tumors should include multiple endoscopic mucosal biopsy specimens. If intestinal metaplasia is present, the improved possibility of survival should influence the surgeon in the choice of operative treatment.     

Urine tissue-polypeptide-specific antigen (TPS) as a marker for bladder cancer.

OBJECTIVES: To determine the sensitivity and specificity of urine tissue-polypeptide-specific antigen (TPS) for bladder carcinomas and to evaluate whether urine TPS is influenced by tumour size, number, grade and stage. PATIENTS AND METHODS: A total of 260 patients entered the study, one group (n = 151) with known bladder cancer disease (79 with recurrent tumour and 72 with no tumour at cystoscopy). The other group (n = 109) consisted of patients without previously known bladder tumour disease, 55 with newly detected bladder tumour(s) and 54 investigated for microhematuria found to be idiopathic. TPS in urine was measured using an ELISA-kit, a solid phase two-site immunosorbent assay with polyclonal antibodies against cytokeratin 18. RESULTS: Urine TPS was significantly higher in patients with bladder tumours (p < 0.001). There was a significant correlation between TPS and tumour size (p = 0.004), grade (p = 0.001) and stage (p = 0.001). Tumour number was not significantly correlated to urine TPS (p = 0.75). With TPS 42 as a cut-off level, the sensitivity was 73% for newly detected tumours and 50% for recurrences; the specificity was 70% and 63% respectively. With a 95% specificity, the sensitivity for newly detected tumours was 33% and for recurrences 18%. The lower sensitivity and specificity for recurrences was mainly explained by differences in tumour size, grade and stage between the recurrences and the newly detected tumours. CONCLUSIONS: Urine TPS is a marker for bladder carcinoma correlated to size, grade and stage. The sensitivity and specificity for newly detected tumours are quite comparable with other markers. Its clinical usefulness is however not established and it appears less useful in the follow-up of patients with known bladder tumour disease.     

膀胱移行细胞癌增殖细胞核抗原表达的研究

采用免疫组化ＬＳＡＢ法对４８例膀胱移行细胞癌增殖细胞核抗原（ＰＣＮＡ）进行检测，发现ＰＣＮＡ增殖指数随肿瘤分级的升高而增高，浸润生长肿瘤ＰＣＮＡ增殖指数明显高于乳头状生长者（Ｐ＜０．００１），ＰＣＮＡ高表达组（增殖指数＞５０％）预后明显差于ＰＣＮＡ低表达组（增殖指数≤５０％）。结果表明ＰＣＮＡ可作为膀胱移行细胞癌恶性程度及预后指标之一。     

c-erbB-2和ki67在胃黏膜肠上皮化生及胃癌组织中的表达

目的:探讨c-erbB-2、ki67在胃黏膜肠上皮化生(肠化)及胃癌中的表达及其与胃癌发生的关系.方法:采用免疫组织化学Envison法对27例单纯肠化(SIM)、26例不典型肠化(AIM)和37例胃癌组织分别进行c-erbB-2、ki67检测.结果:c-erbB-2、ki67在胃癌组织中的表达均高于SIM中的表达(P<0.05),AIM与胃癌组织中的表达差异无统计学意义(P>0.05).结论:c-erbB-2、ki67在AIM及胃癌组织中高表达,AIM与胃癌发生关系密切,属于胃癌的癌前病变.     

Myeloid metaplasia masquerading as a urethral caruncle

A 64-year-old woman presented with a painless bleeding mass of the urethral meatus that was diagnosed as a caruncle and removed surgically. Histological examination revealed a cellular and vascular polypoid lesion that contained megakaryocytes, as well as groups of hematopoietic stem cells, and maturing cells of the erythroid and granulocytic series. The diagnosis of myeloid metaplasia was confirmed by marker studies with immunoperoxidase techniques. The patient had a long history of bleeding and clotting problems owing to a myeloproliferative disorder with thrombocytosis and gradual development of myelofibrosis. No other foci of extramedullary hematopoiesis were apparent. The patient was free of urinary symptoms 22 months postoperatively.     

Serum carcino-embryonic antigen (CEA) and its possible use as tumor marker for secondary tumors in urinary intestinal reservoirs

ObjectivesSerum carcino-embryonic antigen (CEA) has become a useful tumor marker in patients with colorectal adenocarcinoma. Patients who undergo uroenteric reconstruction, such as urinary diversion (UD), have an increased risk of developing malignant changes in their UD. We compared serum CEA levels in patients with different types of UD, evaluating long-term CEA changes and assessing its potential for use as a tumor marker of malignant transformation in the UD.Materials and methodsSerum CEA was evaluated 3 to 122 months after surgery in 177 patients with different types of UD and retrospectively analyzed. The normal range for CEA was 0.2–3.4 μg/l. No patient had a history of colorectal cancer.ResultsA total of 443 CEA samples from 177 patients were evaluated. CEA was elevated (up to 32 μg/l) in 122 samples (27.5%) from 59 patients (33.3%). Patients with Mainz Pouch II had significantly higher CEA levels (P = 0.037) than patients with other forms of UD. CEA levels increased significantly in the study population during follow-up (P = 0.0000007). Five of the patients (2.8%) developed a secondary neoplasm, 4 of whom had elevated CEA. Three neoplasms (urothelial cancer) were located outside the UD. Only 2 tumors were actually located in the UD: an urothelial cancer at the uretero-colonic anastomosis of the UD with normal CEA levels, and a colonic adenoma at the bottom of the UD with elevated CEA levels. No patient had adenocarcinoma in the UD.ConclusionElevated serum CEA is a common finding in patients with UD using bowel segments (33.3%), especially in patients with rectal reservoirs. Serum CEA has a tendency to increase over time in patients with UD but is not a valuable marker of secondary neoplasms in these patients.