Câncer de cólon em adolescentes / Carcinoma of the colon in teenagers

o Carcinoma do cólon é uma entidade infreqüente em pessoas menores de 30 anos. Neste trabalho efetuamos um estudo retrospectivo da sua incidência no Hospital "Miguel Perez Carreño" do IVSS de Caracas, durante os anos de 1973 a 1987, na populaçäo compreendida entre os 12 e 18 anos. De um total de 218 casos, nove pertencem a este grupo etário. Säo discutidos os fatores clínicos, terapêuticos e o prognóstico desta afecçäo

Steroid-hormone receptors in nonpalpable and more advanced stages of breast cancer. A contribution to the biology and natural history of carcinoma of the female breast.

Tumors of five groups of patients, with (1) nonpalpable primary breast cancer, (2) palpable operable primary breast cancer, (3) loco-regionally advanced primary breast cancer, (4) first and (5) late metastatic breast cancer, were studied in respect to their steroid receptor content. A statistically significant decrease of progesterone receptor positive tumors and of tumors positive for estradiol and progesterone receptors, was found with increasing advance of the disease. A reversed extrapolation of these figures supports the hypothesis that every breast cancer contains steroid receptors and is hormone-dependent from its inception.

Local infiltration of T-lymphocyte subsets as a prognostic indicator in patients with nasopharyngeal carcinoma.

We studied tumor-host interactions in 47 patients with NPC. The local infiltration of T-lymphocyte subsets was investigated by an immunoperoxidase technique using monoclonal antibodies. Biopsy specimens of patients without cervical metastasis showed more T-lymphocyte (T11) infiltration. The amount of Leu-3a (helper/inducer) and T8 (cytotoxic/suppressor) cell infiltration did not correlate with the age, sex, clinical stage, and peripheral blood T4 and T8 cells of the patients. A higher incidence of Leu-3a cell infiltration was found in patients with high serum IgA antibody titers to EBV VCA. A trend of better prognosis was revealed in those cases with no or slight stromal T8 cell infiltration. A local immune response was found to exist which may prevent the spread of NPC to the cervical nodes, but this needs further study to evaluate the local infiltration of T-lymphocyte subsets as a prognostic indicator.

Increased fucosylation of high-molecular-weight glycoproteins accompanies retinoic-acid-induced differentiation of F-9 embryonal carcinoma cells.

Retinoic acid (RA) treatment of F-9 embryonal carcinoma cells resulted in cell flattening and increased production of laminin B1 chain, both indicating differentiation to endoderm-like cells. In addition, RA caused a time- and dose-dependent decrease in growth rate in monolayer culture and a dose-dependent decrease in the ability of the cells to form colonies in soft agarose. Differentiation was accompanied by an increase in the fucosylation of specific high-molecular-weight cellular and cell-surface glycoproteins. The fucosylation of glycoproteins of Mr 175,000 (gp175), 250,000 (gp250), and 400,000 (gp400) increased as early as 24 hr after the addition of 5 x 10(-6) M RA to the culture medium. These changes preceded both growth inhibition and the induction of laminin B1 expression, which were detected 48 to 72 hr after addition of RA. The increased fucosylation of these glycoproteins showed a distinct dose-response relationship. Both gp175 and gp250 showed the greatest increase in fucosylation at 10(-5) M, which was also the dose at which RA induced laminin maximally, while the fucosylation of gp400 was greatest at 10(-8) M RA and declined at higher concentrations. The overall synthesis of large fucosylated glycopeptides decreased in RA-treated cells, in spite of the increases in the fucosylation of specific cellular glycoproteins. RA-induced differentiation of F-9 cells was also accompanied by a time- and dose-dependent increase in fucosyltransferase activity. Although the functions of these glycoproteins are not currently known, the early increase in their fucosylation can be considered as a marker of differentiation in this system.

Anaplastic carcinoma of the thyroid. A clinicopathologic study of 121 cases.

One hundred twenty-one cases of anaplastic carcinoma of the thyroid treated at M.D. Anderson Cancer Center, Houston, were reviewed. Anaplastic carcinoma is a rapidly growing neoplasm with a dismal prognosis. The mean survival of our patients was 7.2 +/- 10 months. A significant percentage of our patients (35%) had areas of well-differentiated thyroid carcinoma elsewhere, supporting the hypothesis that anaplastic thyroid carcinoma arises from preexisting well-differentiated thyroid carcinoma. Twenty-four of 30 tumors analyzed (84%) stained for keratin, 28 (93.3%) stained for vimentin, and ten (33%) stained for epithelial membrane antigen. Younger patients lived longer than older patients, and patients whose disease was earlier-stage at presentation responded better than patients with metastases at presentation. Radical surgery alone did not significantly increase survival duration over less radical surgery. The role of multimodality therapy needs further evaluation.

Establishment and characterization of continuous cell line MTC-SK derived from a human medullary thyroid carcinoma.

Tumor cells of a human medullary thyroid carcinoma were isolated and propagated in tissue culture. Several cell lines with different morphology developed from the primary culture, among others a fibroblast-like growing cell line (MTC-F) and a cell line growing as a suspension of single cells and spherical cell clusters (MTC-SK). The MTC-SK cell line was serially propagated for 90 passages, over 3 years. When examined at different times throughout the in vitro period, MTC-SK exhibited properties characteristic of medullary thyroid carcinomas: the cells maintained their epithelioid morphology; endocrine granules were demonstrated in the cytoplasm by electron microscopy; in situ hybridization confirmed the production of calcitonin- and bombesin-mRNA (gastrin releasing peptide); the cells revealed positive immunoreactivity with antibodies to calcitonin, calcitonin gene-related peptide, and bombesin. The in vitro properties of the MTC-SK cells corresponded to the results obtained from the tissue of origin. Cytogenetic studies of the MTC-F cell line revealed a supernumerary metacentric chromosome (20?). In the MTC-SK cell line the predominant findings were terminal chromosomal rearrangements most frequently concerning chromosome 11p, i.e., the locus of the calcitonin and calcitonin gene-related peptide genes and the H-ras oncogene, and a characteristic instability of the centromeric region of chromosome 16 and somatic pairing of the homologous chromosomes 16.

Flow cytometric DNA content analysis of a case of pilomatrix carcinoma showing multiple recurrences and invasion of the cranial vault.

Pilomatrix carcinomas are rare neoplasms of the skin that may be locally aggressive or metastatic. The differentiation of these tumors from benign pilomatrixomas depends on a constellation of microscopic features, some of which may be equivocal or absent in individual biopsy specimens. We encountered a tumor with distinct pilomatrix differentiation (lobulated nests of basaloid cells, ghost cells, focal calcification) that recurred multiple times and ultimately invaded the cranial vault. Despite this aggressive behavior, the tumor was difficult to separate from benign pilomatrixoma on morphologic grounds. Because DNA content flow cytometry has proved useful in the prediction of aggressive behavior in various solid tumors, we analyzed this neoplasm by flow cytometry. Neither aneuploid peaks nor a high proliferative fraction were seen in this example of pilomatrix carcinoma.

Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2.

Several studies have reported effects of gastrointestinal regulatory peptides on growth of experimentally induced pancreatic neoplasms and human cancer cell lines. The growth of human pancreatic cancer lines PANC-1 and MIA PaCa-2 was characterized in vitro, and the effects of cholecystokinin, bombesin, insulin, epidermal growth factor, secretin, vasoactive intestinal peptide, and somatostatin were determined. Fetal bovine serum was required for initiation of growth in both cell lines. Growth effects of peptides were determined by incubating cells with peptides in serum-free medium after a 72-h preincubation in 10% serum-supplemented medium alone. Epidermal growth factor (3.4 x 10(-9) M) and insulin (10(-6) M) significantly (p less than 0.001) increased growth of both cell lines as determined by increases in deoxyribonucleic acid and protein. Bombesin, secretin, vasoactive intestinal peptide, and somatostatin (all 10(-8) M) did not affect growth of either cell line. Neither cholecystokinin-8 nor [Thr4, Nle7] cholecystokinin-9 altered growth in concentrations from 10(-12)-10(-6) M. Anchorage-dependent clonogenic growth of both cell lines was also not altered by cholecystokinin-8. Cholecystokinin added to cultures was degraded by separate effects of serum and cells. Addition of cholecystokinin-8 to cultures every 8 h maintained cholecystokinin levels but did not alter cell growth. These data support roles for epidermal growth factor and insulin as growth factors for human pancreatic cancer cell lines.

Human papillomavirus infection of the uterine cervix analyzed by nonisotopic in situ hybridization.

Some types of human papillomaviruses (HPVs) have been suggested to be strongly related to uterine cervical carcinoma. An attempt to detect these in formalin-fixed, paraffin-embedded sections was made by either immunohistochemical or by in situ hybridization. Anticapsid protein of bovine papillomavirus antibody labeled with peroxidase was used for immunohistochemistry, and biotin was used instead of radioisotopes to label probes for in situ hybridization, which resulted in low background and a rapid procedure. Condylomatous changes were stained immunochemically with this antibody even in invasive carcinoma, whereas the carcinoma itself was not stained. Direct correlation was demonstrated by in situ hybridization between the HPV genome and histopathological structure, which was impossible by Southern or dot hybridization. HPV DNAs were detected in the nuclei of koilocytes and dyskeratinocytes of condylomata and dysplasias. Furthermore, hybridization signals of HPV DNAs in basal and parabasal cells suggested that HPV infection had already begun in the basal cells. In the case of malignant neoplasia accompanied by dysplasia, the same type of HPV was detected both in the malignant neoplasia and accompanying dysplasia. In one case of intraepithelial carcinoma, the very small focus of carcinoma just arisen in the cells of dysplasia was identified, and both were positive for HPV 18. This fact supports the suggestion that the carcinoma arises in dysplasia. Invasive carcinomas were classified further into keratinized, large-cell nonkeratinized, and small-cell nonkeratinized types, and the positive frequency for HPV 16 decreased as the differentiation of the carcinoma decreased. In the case of keratinized type of invasive carcinoma, strong hybridization signals were prominent around the malignant pearl formation.

Imprint immunocytochemistry of estrogen receptors in breast carcinoma.

To clarify the accuracy of immunocytochemical detection of estrogen receptors (ER) in breast carcinomas using cytological materials, imprint specimens from tumor tissue were compared with frozen tissue sections and tumors analyzed by the dextran coated charcoal (DCC) method and enzyme immunoassay (EIA). Out of 50 cases examined by imprint immunocytochemistry, there were 39 ER positive cases (78.0% positivity). The positivity in the imprint materials agreed with that of the DCC in 36 out of 40 cases (85.0%), with 100% sensitivity and 60.0% specificity. The two methods statistically correlated with each other in their positivity and grade (p less than 0.001). The positivity and grades of imprint and frozen immunocytochemistry as well as those of imprint immunocytochemistry and the EIA agreed almost perfectly with each other. As a result of the present study, we concluded that immunocytochemical detection of ER is indeed reliable, as accurate as other procedures. We recommend that aspiration biopsy cytology (ABC) be used for morphological examination and ER immunocytochemistry when adequate materials are available and that imprint materials be used when ABC materials are inadequate and fresh tissue is available at the time of surgery.

Distinct patterns of chromogranin A-related species can be demonstrated in endocrine cells.

We have studied the pattern of chromogranin A (CgA)-related species in different human endocrine cells that produce CgA and also express the calcitonin gene. Antibodies against CgA peptides that span its linear sequence were used in Western analysis of cell lines derived from medullary thyroid carcinoma (MTC), small cell lung cancers (SCLC), epidermoid cell lung cancer (ECLC) and a pulmonary carcinoid tumor (CRND). Each of the cell lines demonstrated a distinct pattern of CgA-related species. Gel filtration studies also revealed multiple and different forms of immunoreactive CgA in the cell lines. Although proteolysis may contribute to our results, these observations suggest that native CgA is processed to smaller species in a tissue-specific pattern by different endocrine cells. More conclusive studies, however, are necessary to establish that cell processing leads to the specific CgA moieties that we have observed.

Immunohistochemical detection of intermediate filament proteins in formalin fixed normal and neoplastic canine tissues.

Normal and well differentiated neoplastic canine tissues were immunohistochemically stained for keratin, vimentin and desmin intermediate filament proteins using commercially available monoclonal antibodies. Keratin was detected in 56 of 57 carcinomas, vimentin in 59 of 62 sarcomas and desmin in three of four muscle cell tumors. Most normal and neoplastic tissues expressed only one type of intermediate filament; exceptions were one hemangiosarcoma and one pulmonary carcinoma in which there was coexpression of vimentin and keratin proteins. Since immunohistochemical detection of intermediate filaments has tissue-specific distribution in the majority of well differentiated canine neoplasms, these stains may be useful in the differential diagnosis of anaplastic canine tumors. However, the monoclonal antibodies to cytokeratin which were tested in this study failed to detect intermediate filaments in liver, pancreas and salivary glands which suggests that these antibodies may also be unable to detect epithelial tumors derived from these tissues. In addition, in nine neoplasms, the normal tissues adjacent to neoplastic cells failed to stain for the intermediate filament normally expressed. When this occurs, evaluation of intermediate filament expression is invalid for the determination of tissue of origin of the neoplastic cells.

[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.

A marker for primary choroid plexus neoplasms.

Primary choroid plexus (CP) tumors are rare neoplasms that present in childhood or, less frequently, in adult life. The majority are benign and amenable to complete surgical excision, but occasionally more invasive variants are encountered. Although generally pathologically distinct, occasionally primary CP neoplasms may be difficult to distinguish from metastatic papillary carcinomas or papillary ependymomas. Conventional cytologic markers are not sufficiently specific to permit accurate diagnosis of primary CP tumors. The authors have reported that the CP is the unique site of synthesis within the brain of transthyretin (TTR, prealbumin), a transport protein for thyroxine and retinol. They therefore investigated the utility of TTR as a biochemical marker for CP tumors. They detected intense immunoreactivity for TTR at high dilutions of primary antiserum in the neoplastic epithelium of all of nine primary CP tumors (six papillomas and three carcinomas), but not in eight cellular or three papillary intracerebral ependymomas, meningiomas, oligodendrogliomas, astrocytomas, primary extracerebral papillary carcinomas (three thyroid, two breast) or five of six cerebral metastases from systemic papillary carcinomas. In one case of cerebral metastasis from papillary thyroid carcinoma, rare isolated immunoreactive cells were observed. Faint staining of the stromal-ependymal junction was seen in myxopapillary ependymomas of the filum terminale, which were otherwise nonreactive. By in situ hybridization, TTR mRNA was abundant in neoplastic CP epithelium, confirming local TTR synthesis. The authors conclude that TTR is synthesized by neoplastic CP epithelium and is an excellent marker for primary CP neoplasms.

Serotonin and 5-hydroxyindoleacetic acid are increased in the sigmoid colon in severe idiopathic constipation.

The distribution of serotonin and dopamine beta-hydroxylase was examined in sigmoid colon specimens from patients with severe idiopathic constipation and control patients with carcinoma of the rectum or colon. Specimens were divided into three regions: (a) the mucosa; (b) the myenteric and submucosal plexuses with the longitudinal and circular smooth muscles; and (c) the circular smooth muscle, for biochemical analysis of serotonin and 5-hydroxyindoleacetic acid (total indoles) and noradrenaline. In both groups of patients, serotonin- and dopamine beta-hydroxylase-like immunoreactivity was localized in nerves in the myenteric and submucosal plexuses, and a sparse innervation was observed in the circular muscle. In addition, intense serotonin-like fluorescence was present in a large number of enterochromaffin cells in the mucosa. Total indole levels were significantly increased in the mucosa (p less than 0.02) and circular muscle (p less than 0.05) of the constipated patients. In contrast, no changes in noradrenaline levels were observed in any of the regions studied. Altered levels of total indoles may thus contribute to severe idiopathic constipation. Analysis of biopsy specimens could be a useful tool in clinical diagnosis and future investigations of diseases of the gut.

Comparison of immunocytochemical and biochemical assays for estrogen receptor in fine needle aspirates and histologic sections from breast carcinomas.

An immunocytochemical assay using a monoclonal antibody specific for estrogen receptor (ER-ICA) was performed on needle aspirates and on histologic sections (mastectomy and biopsy specimens) from 55 patients with breast cancer. A total of 82 ER-ICAs were performed, with matched cytologic and histologic specimens in 27 patients, cytology alone in 15, and histology alone in 13. ER-ICA results were described by a histochemical score (H score) based on intensity-weighted percentages of staining cells. The H scores were compared with results of sucrose density gradient (SDG) analysis of histologic specimens (mastectomy, resection, or biopsy). An H score greater than or equal to 10 and an SDG value greater than or equal to 10 fmol/mg protein were considered positive. The sensitivity of cytologic ER-ICA was 94%, the specificity 100%. The sensitivity of histologic ER-ICA was 67%, the specificity 90%. Correlating cytologic H score with Black's nuclear grade showed that grade 1 (the most anaplastic) carcinomas demonstrated the lowest H scores (mean, 7.3 +/- 29.8), whereas the highest H scores were noted in grade 3 tumors (mean, 150.0 +/- 88.1). Both SDG and ER-ICA showed ER values to be lower in premenopausal than postmenopausal women. There was no correlation between H score and presence of axillary nodal metastases or tumor size. An overall good correlation was demonstrated between immunohistochemical methods and biochemical analysis.

Lectin-resistant variants of mouse Lewis lung carcinoma cells. II. Altered glycosylation of membrane glycoproteins.

Lectin-resistant variants of mouse Lewis lung carcinoma LL2 cell line, selected with wheat germ agglutinin (WGAR), Ricinus communis agglutinin II (RCA IIR) and Aleuria aurantia agglutinin (AAAR) were studied. Total cellular glycopeptides of the parent LL2 line and of the five lectin-resistant variants were analyzed by gel filtration and affinity chromatography on immobilized concanavalin A and Lens culinaris agglutinin. The results revealed that low-metastatic WGAR and RCA IIR variants possessed less highly branched tri- and tetra-antennary N-acetyllactosaminic type glycans with a simultaneous increase in biantennary N-acetyllactosaminic type, oligomannosidic type or hybrid type glycans, as compared to the parent metastasizing LL2 cell line. These findings imply that cell surface carbohydrate changes may possibly be relevant for metastasis. However, the AAAR variant, which possessed reduced spontaneous metastatic ability after s.c. administration, but increased experimental metastatic ability after i.v. inoculation, exhibited apparently the same glycan pattern than the parent LL2 line. This particular variant is under investigation in order to find specific modification(s) of glycan(s) which could play a specific role in the metastatic process.

[The relationship between the receptor status and the mammographic picture in operable breast cancer]. / Relazione tra assetto recettoriale e quadro mammografico nel cancro mammario operabile.

To verify the relationship of mammographic (Mx) patterns of breast cancer to hormone receptor content (ER, PgR) we studied 129 women (59% in postmenopause; average age 55) in the last 3 years. All women had operable breast cancer and were submitted to mammography before surgery. The tumors were classified, according to Mx characteristics, in 5 classes (Broberg, 1983). ER and PgR contents (cut-off for positivity: 10 fmol/mg prot cyt) were analyzed in all patients by means of DCC method. The percentage of ER+ cases was significantly higher in class I than in all other Mx classes (85% vs 57%; p = 0.02), whereas it was lowest in class IV (51% vs 70%; p = 0.03). The percentage of PgR+ cases was significantly different only in class I with respect to class IV (70% vs 41%; p = 0.002). As for ER and PgR mean tumor content, no statistically significant difference was observed between the 5 classes. When the 2 receptors were simultaneously considered the percentage of ER+ PgR+ cases was higher in class I than in all the extant classes (p = 0.01), and the percentage of ER- PgR- was higher in class IV than in the extant ones (p = 0.02). In selected subgroups of patients, Mx classification of breast cancer can help the physician predict the hormone receptor tumor status with sufficient reliability.

Comparative assessment of proliferation and DNA content in breast carcinoma by image analysis and flow cytometry.

Although tumor DNA content and proliferation are usually determined by flow cytometry (FCM), quantitative microscopic image analysis is a viable alternative technique that also provides important histologic correlations. To compare these methods, we measured DNA content and proliferation in 54 consecutive breast cancers and 15 benign breast lesions by FCM and IA. DNA content determination was concordant in 49 of 54 cancers measured by FCM and IA. Four of the discordant cases were aneuploid by IA and diploid by FCM. There was good correlation between the DNA index (DI) measured by FCM and IA (r = 0.89, P less than 0.0001). Proliferation was assessed by IA quantitation of Ki-67 and PCNA/Cyclin antibody staining, as well as by flow cytometric S-phase fraction (SPF). Ki-67 positivity was greater in breast cancer than in benign controls (21.6% +/- 13.1% vs. 7.9% +/- 5.6% [P less than 0.0001]), as was PCNA/Cyclin positivity (10.2 +/- 6.7% vs. 2.7 +/- 2.5% [P less than 0.0001]). S-phase fraction measured by FCM was 7.9% +/- 5.7% for carcinomas and 3.17% +/- 2.1% for benign controls (P less than 0.003). Ki-67 and Cyclin staining, as well as SPF, were significantly increased in aneuploid compared to diploid tumors, and increased staining was associated with worsening nuclear grade. There were significant correlations between SPF and Ki-67 staining (r = 0.48, P less than 0.0001) and SPF and Cyclin staining (r = 0.48, P less than 0.0001). We conclude that FCM and IA provide comparable measurements of DNA content, although occasional discrepancies occur. Image analysis provides a valuable alternative method for assessing tumor cell proliferation and may offer certain advantages over FCM.