Human chorionic gonadotropin and related glycoprotein hormones in lung cancer cell lines.

Twenty-five non-small cell lung cancer (NSCLC), 42 small cell lung carcinoma (SCLC), one extrapulmonary small cell carcinoma, 4 carcinoid, and 13 non-lung cancer cell lines were analyzed for human chorionic gonadotropin (HCG) and related glycoprotein hormones. HCG or its subunits were present in 72% of NSCLC, 10% of SCLC, one extrapulmonary small cell carcinoma, 3/4 carcinoids and 2/13 non-lung cancer cell lines. Related glycoprotein hormones were undetectable. These data indicate a frequent production of HCG or its subunits by NSCLC cell lines and cell lines from tumors with carcinoid features. They confirm the clinical inclusion of carcinoids under the broad category of NSCLC rather than SCLC despite their neuroendocrine features. Clinicians should not assume that undifferentiated NSCLC with HCG production represent germ cell tumors.     

Ectopic hormones in lung cancer patients at diagnosis and during therapy

In roughly 10 patients with lung cancer of various histologic types, the levels of hormones adrenocorticotropin (ACTH), calcitonin, parathormone, beta-choriogonadotropin (HCG), human placental lactogen (HPL), growth hormone (HGH), and prolactin were determined by radioimmunoassay. The ACTH level was elevated in 30% of patients with oat cell carcinoma and in 26% of patients with large cell carcinoma. Calcitonin levels were increased in 48% of patients with oat cell carcinoma. Elevated levels of HCG were found in 33% of patients with oat cell carcinoma, in 26% of patients with large cell carcinoma, and in 19% of patients with squamous cell carcinoma. Parathormone was increased in 32% of patients with squamous cell carcinoma in 27% of patients with oat cell carcinoma, and in a few patients with large cell carcinoma. Prolactin, HCG and HPL were present only in single cases. Elevated levels of at least one hormone were found in 65.2% of all patients, and in 78% of the patients with oat cell carcinoma. Serial determinations of ACTH and calcitonin showed that these hormones are useful for monitoring therapy in lung patients. There was no relation between hormone levels and the clinical stage of disease.     

Tumor-associated antigen levels (carcinoembryonic antigen, human chorionic gonadotropin, and alpha-fetoprotein) antedating the diagnosis of cancer in the Framingham study.

Determinations of carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were done by use of frozen serum samples antedating the diagnosis of cancer for 9 pancreatic and 8 gastric carcinoma patients from the Framingham Heart Study. The longest intervals for elevated antigens before cancer diagnosis were 10 months for CEA and 26 months for HCG. (The single elevated AFP was found in a sample 10 days before clinical diagnosis.) Samples from 31 controls matched with the cancer subjects by age, sex, vital capacity, and smoking status showed over 20% "false" positive CEA elevations (all smokers with low vital capacities) and over 20% borderline false positive HCG elevations in postmenopausal females. Although 10-26 months' lead time could infer some potential for use of these tumor-associated antigens to help detect malignant neoplasms at an earlier stage, a serious problem of frequent false positives prevents CEA and HCG levels from being useful as cancer-screening tests at this time.     

Lung cancer mimicking as pregnancy with pneumonia

SUMMARY: Lung cancer that presents with secretion of beta HCG is rare. We report a case of a young female patient who presented with symptoms of pneumonia and was found to have a positive pregnancy test. With non-resolution of the consolidation and progression of her symptoms she subsequently was found to have large cell lung cancer with ectopic beta HCG secretion. Ectopic production of a variety of hormones such as ADH, parathyroid hormone, ACTH, insulin-like growth factor thus leading to presentation as endocrine syndromes in patients with lung cancer is well known. The presentation of lung cancer mimicking as pregnancy has not been previously reported. This case illustrates the importance of considering the possibility of paraneoplastic secretion of beta HCG in female patients who have a positive pregnancy test in an appropriate clinical setting. This may prevent a delay in the diagnosis and treatment of malignancy in young women.     

Human chorionic gonadotropin in colorectal carcinoma. An immunohistochemical study

To assess the biological significance of human chorionic gonadotropin (HCG) detection in large bowel carcinomas, we have studied immunohistochemically 50 colorectal carcinomas, 20 adenomas, 8 ulcerative colitis, and 10 normal colonic mucosae. The HCG-immunoreactive cells were found in 26 carcinomas (52%). Positivity was not detected in any normal mucosa or benign lesions. Cells containing HCG predominated in mucinous (80%) and poorly differentiated carcinomas (92%). No trophoblastic differentiation could be demonstrated in any tumor. Human chorionic gonadotropin was detected more frequently in carcinomas invading the entire bowel wall (67%) than in those confined to the submucosa or muscularis propria (30%). Fifteen of 19 cases (79%) with lymph node and/or hepatic metastases had HCG in the primary tumor, whereas only 9 of 23 cases (32%) without metastases showed HCG immunoreactivity. The eight patients with hepatic metastases had HCG in the primary tumor. Thus, the immunohistochemical detection of HCG in colorectal carcinomas may be a biological marker of prognostic significance.     

Steroid receptors in dimethylhydrazine-induced colon carcinogenesis

To investigate whether gonadal hormones are involved in the tumorigenesis of dimethylhydrazine (DMH)-induced colonic neoplasms, the authors measured steroid receptors in the neoplasms. 30- or 60-day-old BD-IX rats were injected with 20 mg of 1,2-DMH per kg of body weight once a week for 20 weeks. Fifty-seven rats were sacrificed at 40 to 45 weeks after the initial injection. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) were measured in colonic neoplasms. The total number of colonic neoplasms was 274 among 57 rats, 65.8% in male rats and 34.2% in female rats. The mean number of colonic neoplasms per rat was higher in male rats, i.e., 5.6, compared with 3.5 in female rats. A slightly higher number of colonic neoplasms per rat was seen in the rats that had the initial injection at 30 days of age. The number of large colonic neoplasms with a diameter of more than 1 cm was 77 (28.1%), 74% of which were seen in male rats. Thus, a higher incidence of tumors that were also larger were seen in male rats. Histologic findings showed that 53.6% of the neoplasms were carcinomas. The highest incidence of colonic neoplasms was in the distal colon in both sexes. Most of the well-differentiated adenocarcinoma were seen in the distal colon (82.2%), whereas mucinous carcinoma and undifferentiated adenocarcinoma were prominent in the proximal colon or cecum (56.1%). In rats with a normal colon, low levels of AR and PR were determined; but ER was not found in any regions of the colon. In DMH-induced colonic cancer, the incidence as well as the concentration was higher in male rats (60.6%, 16.9 +/- 3.6 fm/mg protein), compared with female rats (40.0%, 4.6 +/- 0.8 fm/mg protein). Similar incidences and levels of ER and PR were seen in both sexes. There was no relationship between steroid receptors and histologic findings in colonic neoplasms. These results suggest that the gonadal hormones, especially androgens, appear to be involved in DMH-induced colon tumorigenesis in male rats.     

消化系癌中HCG表达及其意义

应用免疫细胞化学方法研究发现部分胃癌（５／４０）、肠癌（４／３２）、胰腺癌（５／４２）、胆囊癌（５／４０）和胆管癌（５／４２）含ＨＣＧ阳性细胞，ＨＣＧ阳性病例多表现为低或未分化癌、组织学分级Ⅲ级和易发生淋巴结或其他器官转移，提示ＨＣＧ阳性消化系癌恶性度高，预后不良。     

A novel high-specificity approach for colorectal neoplasia: Detection of K-ras2 oncogene mutation in normal mucosa

There is an important need for a high-specificity approach to colorectal cancer. Approximately 50% of colorectal tumors contain K-ras gene mutations, which occur as an early step in carcinogenesis. K-ras mutations were detectable not only in tumors but also in microscopically normal colorectal mucosa close to carcinomas in some patients with colorectal cancer. This is the first systematic analysis of K-ras mutations in normal colonic mucosa at multiple consistently-selected locations. A total of 480 normal colonic mucosal samples were obtained from 80 subjects, including 65 patients with sporadic colorectal cancer and 15 controls in whom a colorectal neoplasm was ruled out endoscopically. Normal mucosal samples were obtained at multiple consistently-selected locations using biopsy forceps during colonoscopy. Mutant allele-specific amplification (MASA)-PCR was performed; this could detect a K-ras mutation in normal colonic mucosa even though it was only sparsely present. The K-ras mutation was found in histologically normal mucosa from colorectal cancer patients (20 of 65 cases; 41 of 390 loci) by MASA-PCR, especially frequent (51%; 19 of 37 cases) when the tumor showed a K-ras mutation. In contrast, no mutation was found in normal mucosa from 15 controls (90 loci). K-ras mutation in normal mucosa showed a significant association with the presence of colorectal cancer (p = 0.008). The specificity of the MASA-PCR method for colorectal neoplasms was thus 100%. We conclude that detection of K-ras mutations in normal colonic mucosa might serve as a high-specificity approach to colorectal cancer.     

Evidence for the existence of different types of large bowel tumor: suggestions from the clinical data of a population-based registry

The clinical findings of a population-based colorectal tumor registry have been analyzed to determine elements of supporting or not supporting the existence of different types of large bowel cancer. Age-specific incidence rate of the 409 registered patients rose sharply with increasing age in all segments of the large bowel; however, regarding left colon and rectum, the male: female ratio showed a marked male preponderance, more evident in the more advanced age groups. Histopathology, studied in 87% of patients, revealed adenocarcinoma as the most frequent feature; however, adenocarcinoma with concomitant adenoma (i.e., presumably arising in adenoma) was observed in 14.3% of cancers of the left colon, in 17.7% of rectal tumors, but in only 5.7% of neoplasms of the proximal colon (P less than 0.05 and P less than 0.01, respectively, vs. left colon and rectum). Some histological features (carcinoid and mucinous carcinoma) were observed in right-side tumors only. Analysis of the familial occurrence of cancer showed that a significantly larger proportion of patients with neoplasms located in proximal colonic segments had three or more first-degree relatives affected by (or deceased from) cancer of all sites. Similarly, colorectal tumors among relatives were more frequent in patients with right-side cancer. The location of the 793 polyps observed during 3 years of registration showed that more than 70% of adenomas were located beyond the splenic flexure, overlapping the distribution of cancers. In conclusion, the differences of sex ratio at different colonic subsites, the higher fraction of adenocarcinomas with adenomas in cancer of the more distal tracts of the large bowel, and the more marked familial occurrence of colorectal cancer in patients with right-side neoplasms tend to support the view that cancer of the proximal colon, cancer of the distal colon, and cancer of the rectum may actually be three different types of tumors.     

A case-control study of risk factors for large bowel carcinoma

Two hundred and seven large bowel cancer patients (93% of all cases diagnosed in a defined community between 1965 and 1976) were matched at random with non-cancer subjects of same age, sex, and place of residence. Men with cancer, aged 75 years and younger than, had a more frequent history of work in a local factory handling synthetic fiber than controls (22 versus 10; P less than 0.025). In this factory 45% of cancers occurred before age 60, while this was true in only 24% of cancer cases outside the factory (P less than 0.05). There was a greater tendency for cancers in factory workers to occur in the colon than in the rectum. Heredity was not found to be a risk factor for large bowel cancer. The rate of prior appendectomy was higher in men with colon cancer (P less than 0.05) and the rate of prior cholecystectomy was lower in females with colonic cancer (P less than 0.05). A previous hemorroidectomy was also found more often in males with colonic cancer (P less than 0.05). Long-standing severe constipation was present more often in patients with cancer (P less than 0.01). There was some evidence for a compounding influence of different risk factors, as studied by relative risk ratio. This study confirms the existence of a high risk of large bowel cancer in a group of workers in a synthetic fiber factory and suggests other factors antecedent to large bowel cancer.     

大肠癌患者外周血Th1/Th2的检测及其临床意义

目的 检测大肠癌患者外周血CD+4细胞Th1、Th2细胞因子的表达水平,观察大肠癌患者Th1/Th2漂移的幅度,探讨Th1、Th2细胞因子与大肠癌发生、发展的关系.方法 采取实验对象的清晨空腹静脉血标本,用Th1、Th2细胞因子标记流式细胞技术检测Th1类细胞因子IFN-γ,Th2类细胞因子IL-4,计算Th1/Th2(IFNγ/IL-4),进行统计学分析.结果 大肠癌患者IFN-γ的表达率为(11.7±1.86)%,健康对照组IFN-γ的表达率为(16.4±6.07)%,大肠癌组比健康对照组明显减低,差异有统计学意义(P＜0.05).大肠癌患者IL-4的表达率为(2.8±0.32)%,健康对照组IL-4的表达率为(1.8±0.19)%,大肠癌组比健康对照组升高,差异有统计学意义(P＜0.05).大肠癌患者外周血IFN-γ/IL-4为4.2±0.94,健康对照组外周血IFN-γ/IL-4为9.7±1.11,差异有统计学意义(P＜0.05).结论 大肠癌患者外周血CD+4细胞表达Th2型细胞因子占优势,Th1/Th2平衡失调,向Th2方向漂移,导致机体免疫功能低下,是大肠癌复发或转移的原因之一.     

A serotonin and beta HCG-producing islet cell carcinoma associated with focal nodular hyperplasia of the liver

A 48-year-old woman is described with a pancreatic islet cell carcinoma that had no clinical evidence of hormone production. This neoplasm was removed by radical distal pancreatectomy. Immunohistochemical and extraction studies performed on the tumor tissue revealed that it was producing serotonin and beta HCG. Circulating levels of these hormones were elevated in preoperative serum samples that had been frozen. Beta HCG, a known tumor marker, has remained normal following operation, and this mirrors her clinical course since she has no evidence of disease 1.5 yr after operation. This patient also had focal nodular hyperplasia of the liver. It is possible that the trophoblastic hormone, beta HCG, which was being produced in excess by the islet tumor, may have directly or indirectly caused or facilitated the development of focal nodular hyperplasia.     

Scirrhous argyrophil cell carcinoma of the stomach with multiple production of polypeptide hormones, amine, CEA, lysozyme, and HCG

Sixteen argyrophil cell carcinomas in 59 gastric scirrhous carcinomas were examined histologically, ultrastructurally, and immunohistochemically for polypeptide hormones, CEA, lysozyme, and HCG. In nine of these 16 tumors, polypeptides such as gastrin, somatostatin, and glucagon were demonstrated. Six of these nine tumors contained all three hormones, and three of these six tumors also had argentaffin cells. In all of these 16 tumors CEA were observed. Eight of them had CEA, lysozyme, and acid mucin synchronously. Of the above six tumors containing three peptides, three produced focal HCG. Ultrastructurally, several types of secretory granules were noted. Histologically, these 16 tumors showed poorly differentiated adenocarcinomas or signet ring cell carcinomas. Macroscopically, generalized type was 11 and localized type five. No hormonal syndrome was detected in any of the patients. It was suggested that these scirrhous argyrophil cell carcinomas of the stomach with the multifunction originate from totipotent immature cells of endodermal origin.     

Serum alpha-fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance.

It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a cohort of patients treated with cisplatin combination chemotherapy between 1983 and 1991. A total of 669 patients were studied. Of 352 patients who had an elevated AFP at the start of treatment and for whom we had data at both day 1 and day 8, 101 (29%) had a surge. Of 317 patients for whom we had data for HCG, 80 patients (25%) had a surge. It was found that an AFP surge was a strong adverse prognostic factor for progression [hazard ratio (HR) 2.28, P=0.005]. There was no statistically significant difference in survival (HR 1.65, P=0.13). There was no prognostic significance of a HCG surge, either for progression or for survival. To investigate whether a surge was an independent prognostic factor for progression and survival, multivariate Cox regression models were fitted using the independent prognostic factors for progression and survival and the surge/decline variable. An AFP surge was retained in the final model for progression. A HCG surge was of no prognostic importance for progression or survival. We conclude that an AFP surge has an adverse prognostic significance, independent of pretreatment characteristics.     

Macrocreatine kinase type 2 in the serum of patients with tumors and with nonmalignant colonic diseases

The macrocreatine kinase type 2 isoenzyme (MCK-2) was investigated as a marker for colonic cancer. It was sought in 252 serum samples from 231 patients: 69 with active colonic cancer, 49 in whom colonic cancer had been successfully resected, 58 with nonmalignant diseases of the colon, and 76 patients immediately following colonic surgery. MCK-2 was detected in the serum of 39 of the patients with cancer (57%) and in one patient with diverticulitis. MCK-2 and carcinoembryonic antigen (CEA) were both measured in 47 colonic cancer patients. Both markers were detected in 19 cases, MCK-2 alone in eight and CEA alone in eight. We conclude that MCK-2 is a promising tumor marker for carcinoma of the colon and that its value might be complementary to that of CEA.     

Progastrin Peptides Increase the Risk of Developing Colonic Tumors: Impact on Colonic Stem Cells

Preneoplastic lesions (aberrant crypt foci, hyperplastic/dysplastic polyps) are believed to be precursors of sporadic colorectal tumors (adenomas, adenocarcinomas). Aberrant crypt foci and hyperplastic/dysplastic polyps likely originate from abnormal growth of colonic crypts in response to aberrant queues in the microenvironment of colonic crypts. Thus, identifying factors which regulate homeostatic versus aberrant proliferation/apoptosis of colonocytes, especially stem/progenitor cells, may lead to effective preventative/treatment strategies. On the basis of this philosophy, the role of growth factors/peptide hormones potentially available in the circulation/microenvironment of colonic crypts is being examined extensively. Since the time gastrins were discovered as trophic (growth) factors for gastrointestinal cells, the effect of gastrins on the growth of normal/cancer cells has been investigated, leading to many discoveries. Seminal discoveries in the area of gastrins and colon cancer as it relates to molecular pathways associated with formation of colonic tumors are reviewed and the possible impact on diagnostic/preventative/treatment strategies is discussed.     

Primary gastric choriocarcinoma: immunohistochemistry, postmortem documentation, and hormonal effects in a postmenopausal female

A rare tumor, primary choriocarcinoma of the stomach, occurred in a post menopausal female. The diagnosis was confirmed by autopsy and by immunohistochemical demonstration of HCG in trophoblastic tumor cells. Theories concerning development of this neoplasm are briefly discussed. In addition, this postmenopausal case uniquely permitted examination of the hormonal effects of the tumor on target tissues without the clouding issue of normal menstrual hormones. It appears that the observed estrogen- and progesterone-related tissue responses were not mediated through the ovary; instead, direct tumor production of these hormones is implicated.     

结直肠相关多原发癌临床特点分析

目的研究结直肠相关多原发癌（MPC）的临床特点,并与同期单发结直肠癌（CRC）比较分析,以为早期诊断及治疗提供帮助。方法回顾分析1997年9月至2007年11月收治的病理资料及分期明确的573例CRC及MPC患者的相关临床资料,比较中位生存期（mOS）、肿瘤病理分型、分期、发病部位等。结果573例患者中MPC45例（7．85％）,其中有肠外病灶的MPC好发部位依次是胃、乳腺、卵巢、肺、小肠及其他。肠内多原发结直肠癌（MPCC）病例中,发病部位以升结肠癌最多（34．0％）,而CRC则以直肠癌最多（36．5％）。比较单发CRC与MPC,两者在肿瘤家族史方面无明显差异;中位发病年龄分别为57岁和63岁;有结肠息肉史的MPC患者占20．0％,而单发CRC仅0．9％;单发CRC与MPC的mOS分别为93．7和64．8个月。单发CRC和MPC病理类型都以高一中分化腺癌居多,但MPC中黏液腺癌较多。结论结直肠相关MPC在CRC患者中较常见;MPC特别是MPCC中结直肠息肉更多见;结直肠相关MPC比单发CRC的mOS短,提示结直肠相关MPC的预后可能较单发CRC差;MPCC结直肠息肉多发,肿瘤发病间隔时间短,mOS也短,提示预后较有肠外肿瘤的结直肠相关MPC差。     

LSA、HCG、β2－MG及CEA联合检测对肺癌的诊断价值

 本文检测了94例术前肺癌和34例术后肺癌血清LSA、HCG、β_２-MG和CEA的变化。 结果表明, 肺癌患者这四项指标均较正常人明显升高, 以腺癌最突出。 术后较术前这四项指标均显著下降，而术后复发者HCG、β_２-MG及CEA均明显升高。 Ⅰ到Ⅳ期肺癌各指标均逐渐升高。 LSA对肺癌诊断的敏感性和准确率最高, 次为HCG、β_２-MG。 腺癌中LSA、β_２-MG的血清水平、敏感性和准确率最高, 鳞癌中LSA和HCG最高, SCLC中HCG和β_２-MG最高。这四项指标的联合检测, 有助于肺癌的诊断、鉴别诊断、病情分期及判断术后复发, 值得临床深入研究。     

Alpha-fetoprotein and human chorionic gonadotropin-producing lung cancer

A 73-year-old man had primary lung cancer that produced both alphafetoprotein (AFP) and human chorionic gonadotropin (HCG). The preoperative serum AFP level of 1039 ng/ml decreased to the normal range 8 weeks after surgery. The preoperative serum HCG level of 11 mIU/ml, which temporarily decreased to the normal range after operation, soon increased thereafter. The serum HCG level decreased, however, to the normal range after postoperative mediastinal radiation therapy. During relapse, only the serum HCG level increased gradually to 26,000 mIU/ml 7 weeks before his death. The lung cancer was classified histologically as poorly differentiated adenocarcinoma. Immunohistochemically, AFP was detected in the mononuclear tumor cells of the primary tumor in the lung, and HCG was found in the giant cells of the subcarinal metastatic lymph node. The concanavalin A non-reactive fraction rate for AFP was 81.3%, and appeared to differ from those of hepatocellular carcinoma and yolk sac tumor.