[Immunohistochemical study and lectin distribution of thyroid carcinoma originated from follicular epithelium].

97 cases of thyroid carcinoma originated from follicular epithelium were investigated by using histological and immunohistochemical techniques with special reference to lectin distribution. According to the WHO histological typing of thyroid tumours, these cases were divided into three categories as follows: papillary carcinoma of thyroid (PCT) 56, follicular carcinoma of thyroid (FCT) 31 and undifferentiated carcinoma of thyroid (UCT) 10. Results showed that three different kinds of thyroid carcinoma presented various hormone function and distribution of lectins. The positive rate of Tg immunoreactivity was significantly different between these three kinds of tumour, i.e. PCT greater than FCT greater than UCT. Additionally, the positive rate of T4 and T3 immunoreactivity was lower than that of Tg. Some Gastrin, SS and calcitonin positive cells were also recognized in carcinoma of thyroid. Lectin--binding rate of WGA, PNA, SBA and UEA to 97 cases of thyroid carcinoma and 9 cases of normal thyroid tissue revealed that different lectin had a selective binding activity to various types of thyroid carcinoma and normal thyroid cells. From the data obtained, it seemed that the morphological differentiation of thyroid carcinoma was in correspondence with difference of function, and the extent of cell differentiation may be closely related to the biological behavior of the tumour.

RAS oncogene product expression in normal and malignant oral mucosa.

Proto-oncogenes are important in both normal cellular differentiation and in carcinogenesis. The majority of transforming genes belong to the ras family and the ras gene product has been shown to be elevated in some oral carcinomas. RAP-5 monoclonal antibody was used to determine the expression of the p21ras protein in normal and neoplastic oral mucosa in an immunohistological study. The expression of p21ras protein was generally restricted to acanthous cells with strong staining in normal oral mucosa and well-differentiated carcinomas. In contrast, the p21ras protein was not detected in significant amounts in severely dysplastic lesions and poorly differentiated carcinomas. These results suggest that expression of p21ras is a normal feature of more fully differentiated tissues, both normal and neoplastic, and is not useful as an indicator of cell proliferation or 'malignant potential'.

[Flow cytometric DNA analysis of papillary carcinoma of the thyroid using paraffin-embedded specimens].

A flow cytometric DNA analysis of papillary thyroid carcinomas has been performed on paraffin-embedded specimens, in order to determine the clinical usefulness of this method by defining the degree of the biological malignancy. Fifty-eight patients with papillary carcinomas were followed from 2 to 8 years. They were classified according to their prognosis into three groups: non-recurrent (47 patients), recurrent (5 patients), and a deceased group (6 patients). Aneuploidy was found in 6 (10.3%) of the total 58 patients. It was more frequently detected in the recurrent (40%) and in the deceased (33.3%) groups than in the non-recurrent group (4.3%). Higher proliferating index values were observed in the deceased group than in the recurrent and non-recurrent groups. These results indicate that a DNA analysis, using routine paraffin-embedded materials, is a useful adjunct in the determination of the degree of the biological malignancy of a papillary carcinoma.

[An immunohistochemical study of estrogen receptors in thyroid carcinoma].

Estrogen receptors immunoreactivity (ER-IR) has been examined in 64 cases of human thyroid carcinomas. ER-IR was found to be located in the nucleus of cancer cells and was detected in 30 (57.7%) of 52 papillary carcinomas that were examined. Eleven cases showing a good number of ER-IR positive cancer cells revealed a lowered EORTC index of under 65, and no ER-IR was found in 12 anaplastic carcinomas. These findings indicate that ER-IR might generally bear a similar reciprocal relationship to the malignancy of a thyroid carcinoma.

Papillary-cystic neoplasm of the pancreas. A clinicopathologic study concerning the tumor aging and malignancy of nine cases.

Nine female patients with papillary-cystic neoplasms (PCN) of the pancreas were studied clinicopathologically. The ages of seven of these patients ranged from 8 to 24 years. The remaining two patients, who were 47 and 60 years of age, were considered to have had the onset in their youth. There were few subjective symptoms, and the lesion was most often detected as a palpation of a mass by the patients themselves. Although the prognosis was generally favorable, the two older patients died of metastases. This suggested low-grade malignancy of PCN. The tumors were large (6.9 cm in mean diameter) and encapsulated, and their cross-sections showed an intermingling of solid tumoral areas and cystic necrotic areas. The histologic features of the solid tumoral portion were relatively uniform, with the tumor cells showing solid and pseudopapillary or pseudoglandular proliferation but few mitoses or atypism. Histochemical, immunohistochemical, and electron microscopic examinations showed polymorphic differentiation, which means that part of the tumor cells differentiated into duct epithelium, acinus, and endocrine cells (primary constituents of the pancreas). These findings suggest that the origin of PCN is totipotential primordial cells found in the development of the embryonic pancreas.

Detection of bladder carcinoma in females by flow cytometry and cytology.

The sensitivity of bladder wash flow cytometry (BWFCM), voided urinary cytology (VUC), and cytology of catheterized urine obtained at the time of cystoscopy (CUC) were reviewed on all women evaluated for bladder cancer at Memorial Sloan-Kettering Cancer Center between June 1985 and December 1986. This comprised sixty-four episodes of pathologically proven bladder cancer in 48 women. Considering positive and suspicious results jointly the sensitivities of BWFCM, CUC and 3 VUC were 75%, 64% and 56%, respectively. If only positive results were considered (i.e., suspicious results considered as negative), the sensitivities of BWFCM, CUC and 3 VUC were 64%, 31% and 32%, respectively. The sensitivities of these tests are less than for a predominantly male population, presumably related to the presence of squamous epithelium and greater frequency of pyuria. However, bladder wash flow cytometry and conventional cytology are still a very valuable addition to cystoscopic examination, and the combination of BWFCM with conventional cytology is more sensitive than either procedure alone.

Expression of keratin 19 distinguishes papillary thyroid carcinoma from follicular carcinomas and follicular thyroid adenoma.

Keratin expression with the use of chain-specific monoclonal antikeratin antibodies was investigated in normal thyroid tissue (n = 4), colloid nodules (n = 19), follicular thyroid adenomas (n = 18), follicular carcinomas (n = 10), and papillary carcinomas (n = 12). Frozen sections were stained with monoclonal antibodies M20 (keratin 8), M9 (keratin 18), and LP2K (keratin 19) with the use of the indirect immunoperoxidase technique. The immunohistochemical findings showed that the expression of keratins 8 and 18 was equally extensive in all normal, benign, and malignant lesions tested. In contrast, different staining patterns were observed with the use of monoclonal antibody to keratin 19. Follicular carcinomas were only focally stained with this antibody or were not reactive at all. Keratin 19, however, was present in all the tumor cells of papillary tissues and in a moderate amount of cells of nonneoplastic thyroid lesions and follicular adenomas. In papillary carcinoma, an identical homogeneous expression of keratin 19 was observed in both papillary and follicular structures, which suggests a common cellular origin. These results show that immunohistochemical staining with the use of monoclonal antibody against keratin 19 is useful to distinguish papillary thyroid carcinomas from follicular adenomas and follicular thyroid carcinomas.

Type II estrogen receptors in the papillary cystic tumor of the pancreas.

Two cases of papillary cystic tumor (PCT) of the pancreas were investigated for the presence of estrogen receptors (ERs) and progesterone receptors (PgRs). Both PCT and normal pancreas are able to specifically bind 3H-estradiol. This binding almost exclusively results from the presence of high levels of type II ER, whereas type I ERs were absent or present at very low levels. Both normal and neoplastic pancreas studied immunohistochemically for the presence of nuclear ER had negative results. This could be explained assuming that anti-ER antibodies are specific for type I binding sites. In conclusion, the presence of specific estrogen as well as progesterone binding may explain the sex and age predilection of PCT and suggest a possible hormone sensitivity for this tumor.

[Relation of the serosal invasion mode to a recurrence in advanced gastric carcinomas].

Discussed are the attributable factors affecting the type of carcinomatous recurrence seen in 126 patients who had been operated on for their gastric carcinomas from 1979 to 1982 and who later showed a macroscopically positive serosal invasion (S0) and a histologically ss alpha approximately se invasion and required a curative resection. Forty-six percent of the patients with an ss beta approximately se invasion had a peritoneal recurrence, 21% a liver recurrence, and 33% a recurrence of some other type, whereas those with ss alpha had no such recurrence. Peritoneal recurrence tended to increase with the increase in the length of the serosal invasion and its rates were: one third in serosal invasions of less than 3 cm, one third in invasions of 3 approximately 6 cm and another third in invasions of over 6 cm. The smaller ratio of submucosal length to subserosal length, especially when less than 1.0, meant a greater frequency of peritoneal recurrence. The histologic characteristics of carcinomas that developed a peritoneal recurrence were poorly differentiated, contained INF alpha and had weaker cellular cohesion, whereas those that developed a liver metastasis were well differentiated carcinomas, contained INF beta and had a tighter cellular cohesion.

[Flow cytometric DNA measurements of thyroid carcinomas].

Flow cytometric DNA analysis has been performed using paraffin-embedded tissue blocks from 121 patients with thyroid carcinoma. The incidence of aneuploidy found in thyroid carcinoma was 9 (7.4%), while 112 (92.6%) were diploid. Aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 undifferentiated carcinoma. Of 4 undifferentiated carcinoma patients who subsequently died, only 1 was aneuploid. The 5- and 7-year survival rate for diploid and aneuploid patients were 94% vs 37%, and 91% vs 37%, with significant differences (p less than 0.01). DNA measurements have been found useful in predicting the survival of aneuploid patients, though there remains some discrepancy between the DNA content and the clinical findings in cases of thyroid carcinoma.

[Ornithine decarboxylase activity and polyamine levels in human thyroid tumor tissue].

Production of polyamines such as putrescine (PUT), spermidine (SPD) and spermine (SPM) primarily from ornithine by ornithine decarboxylase (ODC) is correlated with cell proliferation. Polyamine levels and ODC activities were measured to determine the degree of biological malignancy in 186 thyroid tumor tissues. Carcinoma showed significantly higher ODC activity and higher levels of PUT, SPD and SPM than benign tumors. PUT levels showed 2.28 nmol/mg protein in anaplastic carcinoma, 0.66 in papillary carcinoma, 0.11 in follicular adenoma, 0.06 in adenomatous goiter and 0.04 in normal thyroid tissue. Anaplastic and papillary carcinomas showed higher PUT/SPD and SPD/SPM ratios than benign tumors. Poorly differentiated carcinoma showed significantly higher PUT level and PUT/SPD and SPD/SPM ratios than well differentiated carcinoma. No correlation was found among polyamine levels, ages and sex in papillary carcinoma. In female patients with papillary carcinoma, no significant difference in polyamine levels was observed between patients above and below 50 years old. These results suggest that ODC activity and polyamine levels may provide useful information to determine the degree of biological malignancy of thyroid tumors.

Serum and tissue total sialic acid as a marker for human thyroid cancer.

In this study, serum and tissue sialic acid levels in various histopathological types of thyroid cancer were measured and were found to be significantly higher than those measured in the control group. The amount of sialic acid in tissue was 2.8 +/- 1.42 mg/100 mg protein while the serum level was 79.2 +/- 6.6 mg per dl. The rise in tissue and serum sialic acid levels was relatively non-specific with respect to type of cancer as they depend on the tumor burden only. Neither were they related to age, sex or duration of cancer. The serum sialic acid levels increased during the few days following thyroidectomy and returned to normal thereafter. The sialic acid determination appeared to be an important criterion in patient follow-up and evaluating therapeutic response.

Papillary cystic tumor of the pancreas: an immunohistochemical and ultrastructural study of 14 patients.

We report herein the clinicopathological, immunohistochemical and ultrastructural studies on 13 female patients and one male patient with papillary cystic tumors of the pancreas. Their ages ranged from 12 to 60 (mean 25) years. Most patients complained of abdominal mass or abdominal pain. Following complete resection of the tumor, all have remained well for between 3 months and 19 years (maen 5 years). In one patient the tumor was malignant and, 10 years after the initial partial resection, there was a recurrence with involvement of the colon, metastasis to the lymph nodes and venous invasion. Immunohistochemically, most tumor cells were positive for neuron specific enolase, synaptophysin, alpha-1-antitrypsin and vimentin and sometimes for the estrogen receptor related antigen, ER-D5, and the oncogen product of c-Ha-ras, c-Ha-ras P21. Ultrastructurally there were zymogen-like intracytoplasmic granules, intercellular junctions and intercellular spaces. These results support the hypothesis that the tumor originates from undifferentiated cells capable of differentiation toward acinar, endocrine or ductular cells. Estrogen and the c-Ha-ras oncogene presumably are linked to the development.

Correlation of an estrogen receptor-related phosphoprotein with histopathological features in breast cancer.

A series of 65 cases of different histological types of breast carcinoma was investigated for the immunohistochemical location of the estrogen receptor-related, 29 kD phosphoprotein using the ER-D5 monoclonal antibody. The ER-D5 response is heterogeneous in relation to some therapeutic limitations and is correlated with histopathological features of the tumors and survival. The main parameters for evaluation of breast cancers are reviewed, both those that are statistically correlated and those that are not apparently always correlated but are known to have considerable biological meaning, such as the ER-status of tumors.

Immunocytochemical assays in human endometrial carcinomas: a multiparametric computerized analysis and comparison with nonmalignant changes.

Immunocytochemical assay (ICAs) were performed on frozen sections from human endometrial samples (n = 89) including normal endometrium, decidua, hyperplasia with and without atypia, and carcinomas. Monoclonal antiestrogen receptor (ER), anti-laminin (Lam), anti-type IV collagen (Coll IV), and anti-Ki67 were applied with avidin-biotin-peroxidase complex or peroxidase-antiperoxidase complex. The results of the ICAs were evaluated through a computerized system of image analysis referred to as SAMBA. It was shown that this system provided for an accurate reliable and reproducible analysis of ICAs in tissue sections. It is concluded that this multiparametric and standardized method of analysis of ICAs can further be applied in correlations with clinical and biochemical data.

Cytochemical assessments of the nuclear DNA distribution pattern by means of image and flow cytometry in thyroid neoplasms and in non-neoplastic thyroid lesions. A comparative methodological study.

The two most prevalent techniques for cytochemical DNA assessment of the nuclear DNA distribution pattern in neoplastic cells are image cytometry (ICM) and flow cytometry (FCM). The aim of the present study was to compare the results of nuclear DNA assessments, obtained by means of these two methods, in fresh surgical biopsy specimens from the thyroid gland, both in neoplasms and in nonneoplastic lesions. Material for DNA analysis was taken preoperatively by fine needle aspiration (FNA) biopsy from 13 papillary thyroid carcinomas and analyzed by the two methods. Surgical specimens were taken from 48 papillary thyroid carcinomas (one of which showed low differentiated papillary and anaplastic giant cell formations at autopsy), 2 follicular carcinomas, 66 follicular adenomas, 7 medullary carcinomas as well as from the nodules of 17 non-toxic colloid goitres and 19 specimens from the diffusely hyperplastic thyroid parenchyma in patients with hyperthyroidism. For the ICM assessments, FNA biopsies or imprints were made from the macroscopically identified fresh thyroid biopsy specimens; for the FCM assessments FNA specimens from the same region were used. In 155 out of the 159 specimens the results obtained by means of the two methods were the same. The DNA distribution pattern in 106 of the neoplasms and in all the 36 non-neoplastic lesions were of the "euploid" type (i.e. "diploid" or diploid/tetraploid"), whereas that of 17 neoplasms were of the "aneuploid" type. Fifteen of the histopathologically benign follicular adenomas showed a cytochemical DNA distribution pattern that by means of FCM was of the "aneuploid" type.(ABSTRACT TRUNCATED AT 250 WORDS)

Co-existent anaplastic and well differentiated thyroid carcinomas: a nuclear DNA study.

Clonal transformation of well differentiated follicular or papillary carcinomas has been suggested as a mechanism by which anaplastic carcinomas of the thyroid might arise. Of 126 cases of anaplastic (giant cell) carcinomas, 17 (13.5%) contained histologically well differentiated tumour foci within or adjacent to the high grade malignant anaplastic tumour. Cytophotometric DNA analysis after Feulgen staining was performed on 11 cases in order to evaluate ploidy of the anaplastic and the well differentiated tumour cells. The majority of these co-existent carcinomas (9/11) were papillary. All 11 anaplastic carcinomas demonstrated an aneuploid DNA pattern which correlated with a poor clinical outcome (7 of 11 died of disease in less than 6 months). In contrast six co-existent papillary and one co-existent follicular tumours were diploid. These data show that the co-existence of anaplastic and well differentiated carcinoma occurs only rarely and when it occurs only one third of the well differentiated tumours contain aneuploid tumour cells. This suggests that in the majority of cases of anaplastic thyroid carcinoma the malignant cells arise de novo rather than through clonal transformation of well differentiated carcinomas.

Production of monoclonal antibody to thyroglobulin from malignant thyroid carcinoma.

In this study, the production of anti-human thyroglobulin (Tg) monoclonal antibodies was attempted to detect Tg levels in serum and to study the localization of thyroid metastases in patients with thyroid-gland ablation. As a result four clones of hybridoma cell lines were obtained. By means of enzyme immunoassay (EIA) and immunohistochemical method, it was found that one of them, 2G4, produced a monoclonal antibody recognizing a malignant structural change of Tg and other three clones produced monoclonal antibodies recognizing not only the normal human Tg but also the malignant Tg. Our monoclonal antibody, 2G4, will be a hopeful reagent for the diagnosis in thyroid carcinoma.

Verrucous carcinoma in situ of the bladder, not associated with urinary schistosomiasis.

Verrucous carcinoma is a variant of well differentiated squamous cell carcinoma that rarely affects the bladder. The bladder localization of this carcinoma is usually associated with urinary schistosomiasis. In this work we report on a rare case of verrucous carcinoma of the bladder not associated with urinary schistosomiasis. To complete this study, analysis of DNA was carried out on the histologic sections of the tumour.

Verrucous carcinoma of the vulva. A clinicopathologic and immunohistochemical study of five cases.

The clinicopathologic features of five cases of verrucous carcinoma of the vulva and their staining pattern with antikeratin monoclonal antibodies AE1 and AE3 were compared with those of conventional squamous cell carcinoma. Two patients had local recurrences but none died of the tumor. AE1 and AE3 antibodies stained the entire epithelial thickness in both verrucous and squamous cell carcinoma, but in the former the positivity was uniform and homogeneous everywhere, while in squamous cell carcinoma the positivity was extremely disorganized and patchy. The pattern of expression of monoclonal antibodies AE1 and AE3 confirms that verrucous carcinoma is an extremely well-differentiated squamous neoplasm in contrast to squamous cell carcinoma, which is heterogeneous from a viewpoint of differentiation.