Carcinoembryonic antigen and alpha fetoprotein in malignant tumors of the female genital tract.

Circulating carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) levels were measured by radioimmunoassay in 53 patients with carcinoma of the ovary, 16 patients with other malignant genital tumors, and 31 women with nonmalignant diseases of the genital tract. The serum CEA concentration was elevated (greater than 5 ng/ml) in 11 patients with ovarian cancer, 2 patients with endometrial cancer, 1 patient with carcinoma of the cervix, and 1 patient with a benign embryonal cystic teratoma. Elevated CEA levels were found only in patients with advanced malignant disease, while early stages were associated with normal CEA concentrations. AFP levels were normal in all but 1 patient. Both CEA and AFP levels were markedly raised in a case of advanced genital carcinoma arising probably from the ovary. Ascitic fluid of another patient with ovarian cancer contained a high concentration of CEA, giving an identical reaction in immunodiffusion with CEA from colon cancer. The present results indicate that while the increased expression of carcinofetal components takes place in some malignant tumors of the female genital tract, it is usually a late phenomenon.     

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Biochemical and immunohistochemical analyses were done on five cases of gastric carcinoma with excessive production of alpha-fetoprotein (AFP). Histologic and ultrastructural examination of these cases showed conventional poorly differentiated adenocarcinoma of cuboidal or polygonal tumor cells in the medullary area with scattered AFP-positive cancer cells. Comparative studies on serum AFP between these cases and in hepatocellular carcinoma (HCC) or in testicular yolk sac tumor cases using concanavalin A (ConA)-affinity and lens culinalis agglutinin A (LCA)-affinity sepharose columns revealed that the AFP derived from four cases had a high ConA nonadsorping rate and high LCA-reactive fraction similar to that of yolk sac tumor. The AFP from one case had a small LCA-reactive fraction similar to that of HCC. Further immunohistochemical study using several markers for liver cells or germ cell tumor did not show additional evidence of these tumor cells to differentiate into liver cells or yolk sac tumor cells. Thus, this study indicates that AFP-producing gastric carcinomas are not always derived from hepatoid differentiation of the foregut. These gastric carcinomas might be categorized into medullary tumor with gastrointestinal tract-specific AFP.     

Production of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: histologic and immunohistochemical analyses of 35 cases

By immunoperoxidase histochemical staining of formalin-fixed paraffin-embedded sections, the production of alpha-fetoprotein(AFP), albumin(ALB), transferrin(TF), alpha-1-antitrypsin(AAT), and human chorionic gonadotropin(HCG) was examined in 35 operatively resected stomach cancers with elevated serum AFP levels (higher than 20 ng/ml as determined by radioimmunoassay). Cells positive for AFP were found in 19 cases (54%). In 29 cases (83%), some tumor cells contained normal serum proteins (ALB, TF, or AAT). All 19 tumors with AFP-positive cells also stained positively for two or three kinds of normal serum proteins. In some cases, AFP and normal serum proteins were localized in the same cells. There were two cases in which metastatic tumors produced AFP, whereas the primary sites did not. In nine cases (26%), HCG was present in tumor cells and HCG- and AFP-positive cells were coexistent in six tumors. Histologic examination of AFP-producing stomach tumors revealed medullary or papillotubular arrangements with marked nuclear atypia and eosinophilic granular or clear cytoplasms containing no glycogen or mucin. Some tumors with medullary patterns resembled liver cell carcinomas. Concordant phenotypic expression of AFP and normal serum protein production appears to be a general feature of AFP-producing tumors such as liver cell carcinoma, yolk sac tumor, and stomach cancer.     

Alpha-fetoprotein associated with islet cell tumors

Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.     

Immunohistochemical localisation of alpha-fetoprotein (AFP) in germ cell tumours: evidence for AFP production by tissues different from endodermal sinus tumour

20 germ cell tumours have been studied with respect to the presence of alpha-fetoprotein (AFP), using the peroxidase-antiperoxidase (PAP) technique. 6 out of 20 tumours contained elements of endodermal sinus tumour (EST) and were AFP positive. 16 tumours were diagnosed either as pure embryonal carcinomas (6) or as mixed germ cell tumours, containing elements of embryonal carcinoma (10). In 3 of these 16 tumours AFP was localised definitely in the embryonal carcinoma cells; in an additional 6, AFP was also detected but it could not be decided whether AFP was present in embryonal carcinoma cells or in EST cells during early differentiation. In 2 of 7 immature teratomas, AFP was shown to be present in cylindric epithelia. All seminomas (4) studied were AFP-negative. These results show that AFP, which occurs regularly in EST, may also be present in embryonal carcinomas as well as in immature teratomas. Thus, it seems that the immunohistochemical demonstration of AFP by the PAP technique is a suitable method of identifying late stages of embryonal carcinoma or early stages of endodermal sinus tumour during the process of differentiation.     

Pathology of Neuroendocrine Tumours of the Female Genital Tract

Neuroendocrine tumours are uncommon or rare at all sites in the female genital tract. The 2014 World Health Organisation (WHO) Classification of neuroendocrine tumours of the endometrium, cervix, vagina and vulva has been updated with adoption of the terms low-grade neuroendocrine tumour and high-grade neuroendocrine carcinoma. In the endometrium and cervix, high-grade neoplasms are much more prevalent than low-grade and are more common in the cervix than the corpus. In the ovary, low-grade tumours are more common than high-grade carcinomas and the term carcinoid tumour is still used in WHO 2014. The term ovarian small-cell carcinoma of pulmonary type is included in WHO 2014 for a tumour which in other organs is termed high small-cell neuroendocrine carcinoma. Neuroendocrine tumours at various sites within the female genital tract often occur in association with other neoplasms and more uncommonly in pure form.     

Alpha-fetoprotein production by rhabdomyosarcoma of the urinary bladder.

Alpha-fetoprotein has emerged as a useful diagnostic tool for hepatic tumour and tumours of germ cell origin. However, isolated case reports of association of this tumour marker with tumours of the lung and non-germ cell tumours of the ovary are reported. We present a case of a Rhabdomyosarcoma, a generally non-secretory tumour that showed raised levels of AFP in serum and reacted positively for the same in a PAP technique for AFP. Cross striations were visible in many cells on II & E stained sections.     

Renal cell carcinoma producing α-fetoprotein (AFP) with a unique lectins-affinity profile

Renal cell carcinoma (RCC) producing α-fetoprotein (AFP) is a rare entity and merely 7 cases have been reported so far. The present case, a 71-year-old woman, showed a high serum AFP level of 204 ng/ml. The RCC of the autopsied right kidney consisted mainly of spindle-shaped or bizarre sarco-matous tumor cells. AFP was immunolocalized only in the concomitant clear cell component. Concanavalin A (Con A)-nonadsorption rate of serum AFP was 42%, which was an intermediate value between those of yolk sac tumors and metastatic liver carcinomas. Lens culinalis agglutinin (LCA)-affinity study of the patient's AFP showed an unknown peak X, which was eluted between the known peaks 2 and 3. These results suggest a certain structural alteration in carbohydrate moieties of the AFP derived from this RCC. A review of the clincopathologic features of 8 patients with AFP-producing RCC was made to understand the pathophysiology of AFP-producing neoplasms. © Wiley-Liss, Inc.     

Alpha-fetoprotein-lectin binding as a marker of tumour activity or liver damage

To establish whether alpha-fetoprotein (AFP) produced in the early post-treatment phase of a patient with a germ cell tumour of the testis or the ovary originates from the tumour or is due to an underlying disturbance in liver function, the binding of AFP to concanavalin A (Con A) was investigated as a discriminative variable. A two-step assay is described that can distinguish the type of AFP produced at levels as low as 10 ng/ml. A Con A-binding ratio of 12–43% was found in the patients with disseminated germ cell tumours and in patients with AFP-positive gastrointestinal carcinomas. AFP from the liver gives ratios below 10%.     

Alpha-fetoprotein-producing renal cell carcinoma

A case of alpha-fetoprotein (AFP)-producing renal cell carcinoma with multiple bone and lung metastases, but without liver involvement is reported. The stain specific to AFP (avidin-biotin complex) proved the presence of the AFP in the cytoplasms of some cells of the renal tumors. In addition, three other cases of AFF-producing renal cancer recently published in the literature in Japan are reviewed. These four cases indicate that mesoderm-originating malignant tumors such as renal cell carcinomas can produce AFP in some situations. So, AFP is probably more universal than believed, although it is generally a popular and useful tumor marker for hepatocellular carcinomas and yolk sac tumors. The knowledge of the presence of AFP-producing renal cell carcinomas will make a new contribution to the study of the oncogenesis of AFP-producing tumors.     

Problems of interpretation of serum concentrations of alpha-foetoprotein (AFP) in patients receiving cytotoxic chemotherapy for malignant germ cell tumours.

Serial determinations of serum alpha-foetoprotein (AFP) concentrations are well established in monitoring the response to therapy of malignant germ cell tumours. Using a radioimmunoassay (RIA) with a sensitivity down to 2kul-1 the majority (57%) of 28 patients with non-AFP producing germ cell tumours had measurable immunologically-reactive AFP in their serum while on treatment. Follow-up for 11-43 months (mean 27) without evidence of tumour activity indicated that this immunologically-reactive AFP was unlikely to be produced by tumour. In patients where the initial serum AFP was raised prior to chemotherapy the AFP concentration did not fall to the normal range at the end of the treatment in 16 (32%) of 41 patients. Follow-up of these patients for 9-48 months (mean 27) has resulted in 5 (12%) relapses in this group. Serum AFP greater than 20kul-1 three months after stopping chemotherapy was a good indicator of residual active tumour and 4 (57%) of 7 patients in this group relapsed. The production of detectable serum AFP is probably related to the type of chemotherapy used and only 7 (14%) of 51 patients treated for gestational choriocarcinoma had detectable AFP concentrations while on cytotoxic chemotherapy. The problem of interpretation of serum AFP concentration in patients with malignant germ cell tumour stresses the need to determine whether there are differences between AFP produced by germ cell tumours and that produced at other sites as a basis for a sensitive assay system able to discriminate between them.     

A case of alpha-fetoprotein-producing gastric carcinoma with histologic features of embryonal carcinoma

A case of advanced gastric carcinoma in a 75-year-old female with highly elevated serum alpha-fetoprotein (AFP) (9050 ng/ml) is presented. A Borrmann 3 type tumor measuring 7 X 7 cm was located in the gastric antrum and directly invaded up to the radix of the superior mesenteric artery. Neither the preoperative CT scan nor close examination at surgery revealed any evidence of hepatic metastasis. The histological examination showed largely embryonal (atypical-cell) carcinoma. By immunoperoxidase staining, AFP and alpha-1-antitrypsin (AAT) immunoreactivities were identified in some carcinoma cells. Sixteen cases of AFP-producing gastric carcinoma reported in Japan were reviewed.     

Radioimmunoassay of serum alpha-fetoprotein in patients with different maliganant tumors.

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.     

Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms.

Serum alpha-foetoprotein (AFP) and serum carcinoembryonic antigen (CEA) levels were measured, serially whenever possible, in 70 patients attending the Institute of Radiotherapy, Rotterdam, on account of testicular (65) or ovarian (4) germ cell tumours or, in one case, an endodermal sinus (yolk sac) tumour in the mediastinum. In 15 patients the disease was active; in the others it was in remission. Patients with active disease had raised serum AFP levels which correlated well with disease activity; no patient without evidence of active disease had raised serum AFP levels. None of the patients with active disease was found to have raised serum CEA levels. There was no correlation between serum AFP and CEA levels in patients with germ cell neoplasms, but good correlation between serum AFP levels and disease activity. Serum CEA levels did not correlate with disease activity, and serial determinations would therefore not be useful in monitoring progress in this group of diseases.     

Endodermal sinus tumor and mucinous cystadenofibroma of the ovary. Occurrence in an 82-year-old woman

We encountered an unusual ovarian tumor consisting of a mixture of typical endodermal sinus tumor (EST) and mucinous cystadenofibroma that occurred in the ovary of an 82-year-old female patient. The EST component showed the classic histologic features of this tumor. Serum alpha-fetoprotein (AFP) level was not determined. Tumor stains were negative for AFP but positive for alpha-1-antitrypsin. The malignant germ cell component was intimately associated with the benign mucinous component. Focal production of epithelial mucin and carcinoembryonic antigen (CEA) in the EST component suggested a probable association between the two tumor types. The tumor was confined to one ovary, and the patient is disease-free 2 years after surgical therapy. This neoplasm is unique not only for the malignant germ cell component occurring in an 82-year-old woman, but for the unusual combination of tumor types. The pathogenesis is unknown.     

AFP-producing Xp11 translocation renal cell carcinoma: Case report and review of the literature

Alpha-fetoprotein (AFP) is a useful tumor marker for hepatocellular carcinomas and yolk sac tumors. Rare extrahepatic visceral malignancies may be associated with AFP production and those exhibiting a hepatoid differentiation by morphology and immunohistochemical are classified as hepatoid adenocarcinoma. Renal cell carcinoma (RCC) producing AFP is a rare entity. To date, only one case of AFP-producing Xp11 translocation RCC has been reported. We reported another case of Xp11 translocation RCC, in which the tumor cells displayed strong immunostaining for AFP, HepPar1, and GPC-3. Additionally, the other published cases are reviewed.     

Non-Hodgkin's lymphomas involving the female genital tract.

Thirteen female patients with lymphomas involving the genital tract were studied. Their median age was 50 years. There were three cases of stage I disease, one stage II and nine stage IV. The gastrointestinal tract was commonly involved in patients with disease in the ovary. The histology was mostly intermediate or high grade according to the Working Formulation. Immunophenotyping was performed in six patients and they were all B-cell tumours. There appeared to have a strong association between gastrointestinal involvement and ovarian disease. All patients received combination chemotherapy with or without additional radiotherapy and the survival of patients with stage I and II disease appeared to be superior to those with stage IV disease. However, the difference observed did not reach statistical significance because of small patient number. It remains uncertain whether lymphomas of the female genital tract by itself carries a poorer prognosis than the nodal lymphomas of comparable stage and histology.     

Structures of disease-specific serum alpha-fetoprotein isoforms

Alpha-fetoprotein (AFP) is widely used as a serological marker in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT). By application of isoelectric focusing (IEF) disease-specific AFP isoforms can be identified. Three major bands are apparent: + 1 (associated with 'benign' liver disease), + II (associated with HCC) and +III (associated with NSGCT). Recently, we have characterized the predominant glycans of human serum AFP and now report the application of these findings and electrospray ionization-mass spectrometry (ESI-MS) to the determination of the glycan composition of the isoforms present in the sera of 12 patients with HCC and of one patient with NSGCT. ESI-MS allowed simultaneous identification of various AFP glycoforms in purified serum AFP. Seven glycoforms were identified, but with different abundance in the sera of the HCC patients, whereas six glycoforms were identified in the serum from the NSGCT patient. The glycan structures of these glycoforms were deduced from their observed masses. AFP glycoforms carrying a single biantennary complex-type N -glycan appeared as the predominant glycoforms, whereas those carrying both N -glycan and O -glycan appeared as minor glycoforms. Correlation between the abundance of the AFP glycoforms and the IEF band intensity suggested that different degrees in sialylation cause the formation of isoforms. This contention was subsequently supported by the ESI-MS and kinetic in vitro desialylation studies on purified Bands + l and + lI AFPs. Our findings indicate that HCC-associated isoforms (Band + II) represent a group of glycoproteins whose carbohydrate structures are all characterized by being mono-sialylated, whereas those associated with benign liver disease and NSGCT are di- and a-sialo species, respectively. Knowledge of the structure of the tumour-specific isoforms should form an important basis for clinically useful assays.     

An alpha-fetoprotein-producing human gallbladder carcinoma cell line (KMG-C) shows more aggressive biologic behavior than an alpha-fetoprotein-non-producing cell line

We have established a new human alphafetoprotein (AFP)-producing gallbladder carcinoma (GBC) cell line, termed KMG-C, from a 67-year-old Japanese male. KMG-C and its reconstituted tumors in nude mice showed the morphological features of an adenocarcinoma. Functionally, KMG-C secreted AFP, carcinoembryonic antigen, and carbohydrate antigen 19-9, as well as 7 serum proteins, including albumin and C-reactive protein. KMG-C showed more malignant biological behavior than an AFP-nonproducing GBC cell line, KMG-A, established originally from the tumor of the same patient; KMG-C had a shorter doubling time, higher tumorigenicity, and an aneuploid DNA index. Our results suggest that AFP-producing GBC cells may have more malignant biological characteristics than AFP-non-producing GBC cells in GBCs having both of these components.