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PubMed2004

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer.

This study was undertaken to determine the value of tumour microvessel density (MVD) and the expression of p53 and vascular endothelial growth factor (VEGF) as prognostic markers in patients with gastric cancer operated on for cure. In all, 156 patients with curatively resected gastric cancer constituted the basis of this blinded retrospective evaluation. Patients were treated with either surgery alone (n=53) or surgery plus adjuvant chemotherapy (n=103). Tumour MVD, p53 expression, and VEGF expression were assayed using immunohistochemical techniques. After a mean follow-up of 43 months, 64 (41%) patients had died and 55 (35%) patients developed tumour recurrence. Positive correlations between MVD and both p53 (P=0.005) and VEGF (P=0.005) expression were observed. Both MVD >/=100 (P=0.05) and positive VEGF expression (P<0.02) were associated with shorter disease-free survival, and positive VEGF expression (P=0.01) was also associated with shorter overall survival. Multivariate analysis confirmed that, in addition to the pathological tumour stage, lymph node ratio, the extent of lymphadenectomy and perineural invasion, p53 expression, and VEGF expression were independently associated with both disease-free survival (P<0.0005 and 0.02, respectively) and overall survival (P<0.02 and 0.01, respectively). Finally, patients whose tumours did not show p53 expression had a survival benefit compared to those expressing p53 when treated with adjuvant chemotherapy (P=0.01). This investigation demonstrates that p53 expression and VEGF expression are independent prognostic factors for both disease-free survival and overall survival in patients with curatively resected gastric cancer, and that p53 status may also influence response to chemotherapy.

Adult↗
PubMed1993

Listeria monocytogenes-induced gamma interferon secretion by intestinal intraepithelial gamma/delta T lymphocytes.

gamma/delta T cells represent a major proportion of intestinal intraepithelial lymphocytes (IEL), and it has been suggested that these IEL serve as a first immune barrier against microbial invasion and that they do so by destroying infected epithelial cells. In the present study, we confirm that both alpha/beta and gamma/delta IEL from naive mice express potent cytotoxicity and produce gamma interferon (IFN-gamma) after T-cell receptor (TCR) engagement by specific monoclonal antibodies (MAb). Intraperitoneal administration of the anti-gamma/delta TCR MAb GL3 caused downregulation of the gamma/delta TCR in IEL, and IEL from gamma/delta TCR-modulated mice failed to express cytotoxic activity and to secrete IFN-gamma after gamma/delta TCR engagement. In contrast, alpha/beta IEL from such mice were still cytolytic and secreted IFN-gamma. Mice were infected orally with virulent Listeria monocytogenes at doses which caused bacterial invasion through the intestinal epithelia. Although alpha/beta and gamma/delta IEL from these mice expressed high cytolytic activities in antibody-redirected killer assays, target cells pulsed with listerial antigens were not lysed. In contrast, IFN-gamma secretion by IEL from L. monocytogenes-infected mice was induced not only by anti-TCR MAb but also by target cells pulsed with listerial antigens, whereas irrelevant antigens, including heat shock protein 60, did not induce IFN-gamma secretion. Furthermore, the number of IFN-gamma-secreting IEL, as assessed by the enzyme-linked immunospot technique, was increased during listeriosis. gamma/delta TCR modulation by GL3 administration abrogated antigen-induced IFN-gamma secretion by IEL from infected mice. These findings suggest that L. monocytogenes induced IFN-gamma secretion by gamma/delta IEL from mice suffering from intestinal L. monocytogenes infection and invasion. Thus, the data provide evidence for a role of IFN-gamma-secreting IEL in local resistance against listeriosis and perhaps other food-borne diseases.

Animals↗
PubMed1993

Steroid hormone receptor immunohistochemistry and amplification of c-myc protooncogene. Relationship to disease-free survival in breast cancer.

BACKGROUND: It is important to develop parameters that aid in prognosticating which patients with breast cancer are more likely to have a rapid disease course and therefore might benefit from early aggressive therapies. METHODS: Specimens from two groups of women, deliberately selected because their clinical courses differed greatly, were studied to detect amplification of the protooncogenes c-myc, int-2, and C-erbB-2/neu by slot-blot assay, the estrogen receptor (ER), and the progesterone receptor (PR) by both biochemical and immunohistochemical procedures (ERICA and PRICA). One group of 50 patients had a prolonged disease-free interval after initial surgery (mean, 6.4 years); the other group of 52 women had had rapid disease recurrence (mean, 1.4 years) or progression (5 patients died of disease within 1 year of diagnosis). The patients were selected from 1700 consecutively accessioned cases if they fit the study criteria and sufficient tissue was available for oncogene hybridization studies. RESULTS: The two groups differed statistically by stage, number of involved axillary lymph nodes, ERICA and PRICA results (P = 0.001), and amplification of c-myc (P = 0.003). The percentage of patients with rapid disease recurrence and progression increased from 0-93% when risk factors changed from best case (ERICA and PRICA results, positive; c-myc, not amplified; and axillary nodes, not involved) to worst case (ERICA and PRICA findings, negative; c-myc, amplified; and axillary nodes, involved). CONCLUSIONS: Women with these worst-case parameters were more likely to have a recurrence sooner and rapidly progressive disease. They might benefit from early aggressive therapeutic measures.

Adult↗
PubMedDate not supplied

[Musculocutaneous and visceral cysticercosis: a rare disease?].

The aims of the present study were to measure the frequency of cutaneous, muscular and visceral forms of cysticercosis in anatomopathological examinations and necropsies in the Federal District and to study the clinical aspects of this disease. In 64.911 protocols of anatomopathological examinations reviewed, 30 (0.05%) had the diagnosis of cysticercosis, 90% had cysticerci in the subcutaneous tissue, skeletal muscle or mucous membrane, 3.3% in lymph node and 6.7% in the central nervous system. Two (7.4%) patients had cysticerci in the tongue. In 1520 autopsies protocols reviewed, 25 (1.6%) autopsies with cysticercosis were found. 96% had cysticerci in the central nervous system, 8% in the heart, 8% in the skeletal muscle and 4% in the liver, either isolated or associated with cysticerci in other viscera. 1122 people were also examined. Indirect immunofluorescence and ELISA were the serological tests used in all patients for the diagnosis of cysticercosis. The radiological investigation of the skull and soft tissues was also performed. 59 (5.3%) patients had both serological tests positive (10 had also biopsies with the diagnosis of cysticercosis). The muscular form was found in 42.4%, subcutaneous cysts were present in 20.3% and the visceral form was found in 3.4% of cases. In patients with visceral cysticercosis, the cysts were localized in the heart, pleura, kidney and ovary. Calcifications in the skull and/or soft tissues were demonstrated radiologically in 32 (2.8%) patients with negative serological tests for cysticercosis. The present study suggests a high frequency of subcutaneous and muscular forms of cysticercosis in the Federal District. The visceral form of the disease is also found in various organs, without clinical manifestations of importance.

Adolescent↗
PubMed2003

Biochemical recurrence without PSA progression characterizes a subset of patients after radical prostatectomy. Prostate-specific antigen.

OBJECTIVES: To characterize a subset of patients with biochemical recurrence after radical prostatectomy but with little, if any, subsequent rise in serum prostate-specific antigen (PSA) and no clinical progression during long-term follow-up. METHODS: Of a series of 600 patients, 158 with biochemical recurrence after radical prostatectomy were examined. We identified a subset with measurable serum PSA levels during long-term follow-up, but with very low PSA velocity and no clinical recurrence. Serum PSA was measured with the ultrasensitive TOSOH assay with a PSA recurrence defined as a serum PSA of 0.07 ng/mL or greater. RESULTS: We identified 14 patients (8.8% of biochemical recurrences) with a detectable serum PSA level after radical prostatectomy yet without clinical or PSA progression at a mean follow-up after radical prostatectomy of 10.3 years. The mean time to PSA recurrence was 5.8 years, and the mean PSA velocity after recurrence was 0.028 ng/mL/yr. No clinical or pathologic features were found that could be used to identify this subset of patients. CONCLUSIONS: A subset of patients with biochemical recurrence after radical prostatectomy will not exhibit a progressive rise in serum PSA or clinical progression at 10 years follow-up. This suggests that serum PSA kinetics should be observed after biochemical recurrence before adjuvant hormonal therapy or radiotherapy.

Aged↗
PubMed1982

Tumor sponge implantation: an in vivo method for studying syngeneic, primary antitumor lymphocyte responses.

Sponge matrices surgically implanted in the s.c. space of the back of normal BALB/c mice were injected with a "regressor" dose of Moloney virus-induced BALB/c tumor cells. The kinetics of the generation of cytotoxic cells within the sponge was studied over a 22-day period in a short-term 51Cr release assay. Cytotoxic activity peaked on Day 16 and then declined to negligible levels by Day 22. No cytotoxicity was detectable when nontransformed BALB/c blast cells, Moloney leukemia virus-induced tumor (LSTRA) cells, or unrelated chemically induced tumor (EL4) cells were used as targets. When the cellular composition of implanted tumor sponges was examined on Day 16, it was found to be 30 to 40% myeloperoxidase-positive cells, 15 to 25% surface immunoglobulin-positive cells, and 40 to 50% theta-positive cells. Treatment with anti-Thy 1.2 plus complement eliminated the cytotoxic response on Day 16. The ratio of T-cells to tumor cells within the sponge was determined by immunofluorescence. Kinetic studies showed that the number of theta-positive cells increased well before cytolytic activity was detected, possibly reflecting increasing numbers of amplifier T-cells or cytotoxic cell precursors. A later decline in theta-positive cells correlated directly with decreased cytotoxicity. Furthermore, onset of cytotoxic activity also correlated with a decline in the percentage of Moloney murine sarcoma virus tumor cells within the sponge. Sponge cells isolated on Day 16 (peak cytotoxicity), mixed with lethal dosages of moloney murine sarcoma virus tumor cells, successfully neutralized the lethal challenge demonstrating the in vivo antitumor efficacy of these effector cells. Sponges were also implanted in mice which had been immunized with single injection of Moloney murine sarcoma virus cells. Inoculation of the sponge with tumor cells resulted in a second set response in which cytotoxic cells appeared much earlier than in unsensitized animals. Cells from spleen, lymph node, or peritoneal cavity of normal or presensitized animals with tumor sponge implants were not cytotoxic, suggesting a highly localized response.

Animals↗
PubMed2006

Protein levels of tissue inhibitor of metalloproteinase-1 in tumor extracts as a marker for prognosis and recurrence in patients with gastric cancer.

BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) correlates with tumor progression in patients with gastric cancer; however, the clinical significance of TIMP-1 as a marker for prognosis and recurrence has not been fully clarified. METHODS: TIMP-1 protein was measured by an enzyme-linked immunosorbent assay in tumor samples from 86 patients who had undergone surgical resection. An intratumoral TIMP-1 value of 10.0 ng/mg protein or more was defined as positive. Patients were followed up for more than 5 years prospectively. RESULTS: Thirty-one of the 86 patients (36.0%) were positive for TIMP-1. Kaplan-Meier curves for overall survival were significantly different between patients who were positive and those who were negative for TIMP-1. Univariate analysis of factors affecting overall survival showed that depth of tumor invasion; lymph node metastasis; peritoneal dissemination; lymphatic invasion; venous invasion; Lauren classification of histology; curability; and TIMP-1 were statistically significant. Stepwise multivariate analysis for overall survival demonstrated that depth of tumor invasion, nodal metastasis, peritoneal dissemination, and TIMP-1 remained independent prognostic factors. Kaplan-Meier curves for disease-free survival were significantly different between patients who were positive and those who were negative for TIMP-1. The incidence of recurrence was significantly higher in patients positive for TIMP-1 than in those who were negative for TIMP-1. The frequency at each site of recurrence was higher in patients positive for TIMP-1. CONCLUSION: These results suggested that the protein concentration of TIMP-1 in the tumor extracts was a useful marker for overall survival, disease-free survival, and disease recurrence in patients with gastric cancer. Thus, tumor TIMP-1 may serve to identify a high-risk group, for whom optimal surgical and medical treatment can be given.

Biomarkers, Tumor↗
PubMed2004

Local and systemic immune responses to Echinococcus granulosus in experimentally infected dogs.

Local and systemic immune responses were studied in six dogs experimentally infected with the dog/sheep tapeworm Echinococcus granulosus. All dogs developed similar IgG antibody response to parasite antigens. In contrast, IgE and IgA responses differed widely. No relationship between IgA responses and parasite burden at the end of the infection were observed. Further, clear differences in the anti-parasite IgA response in serum as compared with specific IgA forming cells in mesenteric lymph nodes were observed within the same dog. An inverse association of anti-parasite IgE and parasite load seemed to be present, with the strongest IgE response in the one dog that had no worms in the intestine at the end of the experiment. No differences were observed in the numbers of intestinal mast cells and goblet cells among all infected dogs. However, the dog with no detectable parasite load had a marked reduction of detected mast cells in the submuscular and muscular layer of the mucosa. Our data give new insight into the immune response of dogs during E. granulosus infection and provide information that may be useful for the rational design of vaccines for the control of hydatid disease.

Animals↗
PubMed1995

Photonic detection of bacterial pathogens in living hosts.

The study of pathogenic processes is often limited to ex vivo assays and cell-culture correlates. A greater understanding of infectious diseases would be facilitated by in vivo analyses. Therefore, we have developed a method for detecting bacterial pathogens in a living host and used this method to evaluate disease processes for strains of Salmonella typhimurlum that differ in their virulence for mice. Three strains of Salmonella were marked with bioluminescence through transformation with a plasmid conferring constitutive expression of bacterial luciferase. Detection of photons transmitted through tissues of animals infected with bioluminescent Salmonella allowed localization of the bacteria to specific tissues. In this manner progressive infections were distinguished from those that were persistent or abortive. We observed patterns of bioluminescence that suggested the caecum may play a pivotal role in Salmonella pathogenesis. In vivo efficacy of an antibiotic was monitored using this optical method. This study demonstrates that real time non-invasive analyses of pathogenic events and pharmacological monitoring can be performed in vivo.

Animals↗
PubMed1971

Properties of adenylate cyclase of lymphoid cells.

Adenylate cyclase of homogenates or lysates of mouse and rat lymphoid tissues was activated by the addition of fluoride ion, epinephrine, or norepinephrine, but not by any of several other hormones. The catecholamine stimulation was characterized as beta-adrenergic. This activity was localized in the small lymphoid cells, was greater in thymic than in splenic or mesenteric node cells, and also was greater in mouse than in rat cells. Catecholamine-stimulated activity of mouse thymocytes remained constant from the 17-19th day of fetal development to 5 weeks after birth; it subsequently decreased to about one-half of the activity by 7-8 weeks. Similar decreases with age occurred in mouse spleen and rat thymus. In contrast, the glucagon-stimulated activity of rat liver increased during a similar period. Hypophysectomy of rats at 3 weeks did not influence the amount of cyclase activity of thymocytes assayed at 7 weeks. When intact mouse thymocytes were first incubated in a culture medium at 37 degrees C with epinephrine or norepinephrine, a second addition of catecholamine after cell lysis no longer stimulated the enzymes. This loss of stimulation was selective, since basal activity and stimulation by fluoride ion were not affected. Incubation of intact cells with phytohemagglutinin markedly decreased the activity of lysates, whether assayed in the presence or absence of catecholamine or fluoride. In contrast, phytohemagglutinin added directly to the assay had no effect. No alternations occurred in adenylate cyclase activity as a result of the incubation of a 1:1 mixture of thymocytes from two strains of mice selected for the capacity of the cells to produce a mixed lymphocyte response.

Adenine Nucleotides↗
PubMed2001

Interleukin 2-antibody and tumor necrosis factor-antibody fusion proteins induce different antitumor immune responses in vivo.

Two fusion proteins, composed of interleukin 2 (IL-2) or tumor necrosis factor (TNF) coupled to an antibody [fusion protein (FuP); IL-2-FuP or TNF-FuP], were capable of retarding growth of a human malignant melanoma in the severe combined immunodeficient mouse depending on the concomitant application of human peripheral blood leukocytes. Here we have analyzed the mechanisms that determine the therapeutic effect. Tumor-bearing severe combined immunodeficient mice received once per week an i.v. injection of HLA-matched peripheral blood leukocytes and twice per week i.v. or intratumoral injections of FUPS: Leukocyte recovery and their activation state were monitored. The number of draining lymph node cells (LNCs) and tumor-infiltrating leukocytes increased continuously, and the yield of draining LNCs was improved significantly when the FuPs were applied locally. In IL-2-FuP-treated mice, the majority of draining LNCs and tumor-infiltrating lymphocytes expressed T-cell activation markers and IL-2, thus being classified as T helper type 1 cells. These cells displayed strong proliferative activity and initiated activation of lymphokine-activated killer cells and CTLS: TNF-FuP supported activation of CTLs and of monocytes as revealed by TNF expression and cytostatic activity. Neither the antibody, nor IL-2, nor TNF, nor the mixture of antibody and cytokines exhibited the full-fledged activational potency of the FUPS: Notably, activation of immune effector mechanisms was much stronger when the FuPs were applied intratumorally. This is the first report to show that FuPs are efficient immunostimulants in vivo for native leukocytes. Although IL-2-FuP induced a T helper type 1 response with recruitment of LAK and CTL, TNF-FuP efficiently recruited and activated monocytes and, in a less pronounced manner, CTLS:

Animals↗
PubMed2000

[Tuberculosis and human immunodeficiency virus infection: clinical manifestations and performance of diagnostic procedures according to distinct forms of the localization of disease].

OBJECTIVES: To analyse the clinical manifestations and performance of the diagnosis methods in tuberculosis (TB) diagnosed in patients with human immunodeficiency virus infection (HIV), according to the location forms of disease (LF). MATERIAL AND METHODS: We revised 80 cases of TB diagnosed in patients with infection by HIV. The data were gathered in relation to TB location, the clinical data and the microbiological and histological diagnosed studies. In the statistic analysis the values p < 0.05 were taken into account. RESULTS: The prevalence of LF was: 1) pulmonary forms (PF) 32 (40%), of which 12 were typical pulmonary (TP) and 20 atypical pulmonary (AP); 2) mixed forms (MF) 21 (26%); 3) extrapulmonary forms (EF) 19 (24%), of which 17 were lymphadenitis; 4) miliary tuberculosis (MT) 8 cases (10%). The prevailing symptoms were: fever (71%) mainly in MF and MT, cough (69%), with less frequency in AP, EF and MT (p < 0.05) and adenomegalies especially in EF and MF. The diagnosis was based on the study of the sputum smears and lymph node. The bacilloscope of the spontaneous sputum was 53% with a minor performance in the AP (p < 0.05), while in lymph node the smear for AFB was positive in 78% cases and caseous granulomas were observed in 87%. CONCLUSIONS: In our study the major confirmed locations were pulmonary and lymph node, the most important clinical symptoms were fever, cough and adenomegalies. The diagnosis was based, in the most of cases, on the microbiologic and histologic examination of bronchial secretion and lymph node samples.

AIDS-Related Opportunistic Infections↗
PubMed2003

Complete tumour regressions induced by vaccination with IL-12 gene-transduced tumour cells in combination with IL-15 in a melanoma model in mice.

In the present study, IL-12 gene-transduced B78-H1 melanoma cells (B78/IL-12) were used in combination with IL-15 to treat melanoma-bearing mice. Genetically modified B78/IL-12 cells, when injected subcutaneously, induced strong activation of antitumour mechanisms resulting in complete loss of tumourigenicity. In a therapeutic model, intratumoural injection of irradiated B78/IL-12 cells significantly delayed tumour growth and led to the regression of melanoma in one case. Similarly, consecutive daily injections of IL-15 markedly inhibited tumour progression with occasional curative effects. When used in combination, vaccination with B78/IL-12 cells and treatment with IL-15 caused eradication of established tumours in all treated mice. The combined treatment with B78/IL-12 cells and IL-15 activated not only a local response against tumour, but also induced systemic antitumour immunity that led to a delay or inhibition of tumour development at a distant site. In vitro studies demonstrated that when used together, B78/IL-12 cells and IL-15 induced a shift from a type Th2 to a type Th1 response. Activation of the antitumour immune response in double-treated mice resulted, in part, from stimulation of IFN-gamma production and was accompanied by the development of cytotoxic effectors in the spleen. As shown in a macrophage tumouricidal assay, macrophages could also play a role in the antitumour effects. The results confirmed that vaccination with IL-12 gene-modified tumour cells is superior to the treatment with unmodified tumour cell vaccine and, additionally, showed that IL-15 is an excellent candidate for adjuvant therapy, inducing synergistically not only a delay of tumour growth but also its complete eradication.

Animals↗
PubMed2005

Protection of gnotobiotic pigs against Salmonella enterica serotype Typhimurium by rough mutant of the same serotype is accompanied by the change of local and systemic cytokine response.

We have demonstrated that severe systemic disease caused by virulent LT2 strain Salmonella enterica serotype Typhimurium in gnotobiotic piglets can be alleviated by oral inoculation with an avirulent rough (R) mutant of the same serotype 24 h before challenge with the virulent strain. Protected piglets had no signs of enteritis. The concentrations of TNF-alpha, IL-1beta, IL-8 and IL-10 were measured by ELISA in ileal washings and plasma of uninfected and infected pigs. The cytokines were not detected in plasma of germ-free piglets, and low concentrations of IL-1beta and IL-8 were found in their ileal washings. The pre-inoculation of the rough mutant induced an increase in IL-8 and decrease in IL-1beta and IL-10 in plasma. The virulent LT2 strain induced very high TNF-alpha concentrations in the ileum which were reduced in the pigs pre-inoculated with the R mutant.

Animals↗
PubMed2003

Follow-up of thyroid cancer patients with "poor prognosis".

High-risk differentiated thyroid carcinoma is the most frequent thyroid tumor of "poor prognosis": this mainly includes patients with extra-thyroidal invasion, or distant metastases, younger patients (<16 years old), and older patients (>45 years old). Among them, metastatic patients with multiple organ involvement at the time of initial diagnosis have the higher risk of cancer death. Additionally, certain histological subtypes are classically more aggressive, and bilateral cervical lymph-nodes metastases or mediastinal involvement may also impart a poorer overall prognosis. More aggressive therapy to produce undetectable thyrotropin levels is usually recommended, although the benefit of such therapy and how long to maintain thyrotropin suppression has not been definitively established. As about two-thirds of the recurrences occur within the first decade after initial treatment, this first decade seems particularly critical, even if follow-up is necessary throughout the patient's life as recurrences may also occur over several decades. Coupled thyroglobulin (Tg) and Tg antibody (TgAb) assay is the first-line tool in their follow-up. Tg measurement obtained either after LThyroxine withdrawal or rhTSH stimulation may permit the selection of patients for scanning with a high dose of 131-I. When either basal Tg level is high or TgAb increases, it appears preferable to schedule patients directly for 131-I therapy followed by a post-therapy WBS. Therefore, the discovery of foci of 131-I uptake is possible in 60 to 80% of such patients. 131-I therapy is proposed as long as metastases trap 131-I without any limit to the cumulative dose of 131-I, although the risk of leukemia rises slightly above a 500 mCi (18,500 MBq) cumulative dose. But when 131-I post therapeutic WBS is negative, any further administration of 131-I is not justified. Alternative imaging procedure is thus required to detect metastases that have lost their capacity to concentrate 131-I. Conventional imaging with ultrasonography of the neck, a CT scan or an MRI of the neck and the chest and bone imaging, and even non-conventional imaging with other isotope procedures, such as 18-FDG whole-body scanning, are nowadays indicated. The goal is to localize those metastases in order to propose the more adequate therapeutic options.

Autoantibodies↗
PubMed2001

Molecular quantification and mapping of lymph-node micrometastases in cervical cancer.

BACKGROUND: A proportion of patients with cancer and lymph nodes negative on histology will develop recurrence. Reverse-transcriptase PCR (RT-PCR) is a highly sensitive method for detection of lymph-node micrometastases, but accurate quantitative assessment has been difficult. METHODS: We studied primary tumours and 156 lymph nodes from 32 patients with cervical cancer (stage IA2, IB1, and IB2) and 32 lymph nodes from nine patients with benign disease. A fully quantitative, real-time RT-PCR assay was used to document absolute copy numbers of the epithelial marker cytokeratin 19. Primers and probe were designed not to amplify either of the two cytokeratin 19 pseudogenes. FINDINGS: All primary tumours and histologically involved lymph nodes (six) had more than 106 copies of cytokeratin 19 mRNA per microg total RNA. Expression of cytokeratin 19 (up to 1.1 x 10(5) copies per microg RNA) was detected in 66 (44%) of 150 histologically uninvolved lymph nodes, and in nodes from 16 of 32 patients with cervical cancer. 15 of these 16 patients with evidence of micrometastases had the highest cytokeratin 19 transcription level in a first lymph-node drainage station (three obturator, six internal, and six external iliac node). Transcription of cytokeratin 19 was found at a low level in just one of 32 lymph nodes obtained from nine patients with benign disease. Median copy number of cytokeratin 19 transcription was significantly higher (>10(3) copies) in association with adverse prognostic features. INTERPRETATION: The results suggest that about 50% of early-stage cervical cancers shed tumour cells to the pelvic lymph nodes. The amount of cytokeratin 19 expression was related to clinicopathological features. Further studies are required to document the clinical implications of molecular micrometastases.

Adult↗
PubMed2003

Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases.

PURPOSE: To determine whether progesterone receptor (PgR) status provides additional value to estrogen receptor (ER) status and improves prediction of benefit from endocrine treatment among patients with primary breast cancer. PATIENTS AND METHODS: Clinical outcomes of patients in two large databases were analyzed as a function of steroid receptor status. The first database (PP), contained 3,739 patients who did not receive any systemic adjuvant therapy and 1,688 patients who received adjuvant endocrine therapy but no chemotherapy. The second database (SPORE), contained 10,444 patients who received adjuvant endocrine therapy but no chemotherapy. Biochemical ER and PgR assays were identically performed in two different central laboratories. RESULTS: In univariate and multivariate analyses, the prognostic significance of PgR status among systemically untreated patients is modest. Among endocrine-treated patients, however, multivariate analyses, including lymph-node involvement, tumor size, and age, demonstrate that PgR status is independently associated with disease-free and overall survival. For recurrence, the reduction in relative risk (RR) was 25% for ER-positive/PgR-negative patients and 53% for ER-positive/PgR-positive patients, compared with ER-negative/PgR-negative patients (P <.0001, PP patients). Patients with ER-positive/PgR-negative tumors have a reduction in RR of death of 30% (SPORE patients) and 38% (PP patients), compared with patients with ER-negative/PgR-negative tumors (P <.0001). For ER-positive/PgR-positive tumors, the reduction of the risk of death was greater than 46% in SPORE patients and 58% in PP patients, indicating that ER-positive/PgR-positive patients derive more benefit from endocrine therapy (P <.0001). CONCLUSION: When accurately measured, PgR status is an independent predictive factor for benefit from adjuvant endocrine therapy. Therefore, PgR status should be taken into account when discussing RR reductions expected from endocrine treatment with individual patients.

Adult↗
PubMed2004

[Expression of estrogen and progesterone receptors and oncoprotein HER-2 as a marker for clinical course and outcome in endometrioid adenocarcinoma of the uterine body (immunohistologic study)].

A retrospective immunohistological assay identified estrogen (ER) (72%) and progesterone (PR) (71%) receptor content in tumors from 76 patients with endometroid cancer (ER+ PR(+)--63.2%; ER- PR(-)--22.3%; ER+ PR- 9.2%; ER- PR+ -5.3%). Pattern R+ involved well differentiated cells, slight invasion of the myometrium and infrequent spreading to the regional lymph nodes, as compared with cases of unidentified ER or PR. Five-year survival in patients with ER+ PR+ tumors was 83% vs. 53% in cases without steroid hormone receptor expression (p = 0.04). HER 2 overexpression was found in 31.6% of tumors involving a decrease in total survival from 73 to 54.2% (p = 0.04). No significant correlation was established between ER and PR, on the one hand, and HER 2 expression, on the other. HER 2 overexpression leveled off the prognostic value of steroid receptor expression to a considerable degree; relapse incidence in patients with HER 2 overexpression in ER+ PR+ tumors rose 9-26.7% while five-year survival dropped 88-60% (p = 0.03). A distinct correlation between ER and PR expression (r = 0.96) was reported by D.C. Alfred et al. and verified by the H-scor procedure (R.A. Mc Clelland et al.). This procedure for steroid receptor expression determination is as the first unsophisticated, yet informative, method.

Adenocarcinoma↗