Tumors In Older Patients Research Articles

In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: a case report

BackgroundThe molecular characteristics and the clinical disease course of bladder cancer (BC) in young patients remain largely unresolved. All patients are monitored according to an intensive surveillance protocol and we aim to gain more insight into the molecular pathways of bladder tumors in young patients that could ultimately contribute to patient stratification, improve patient quality of life and reduce associated costs. We also determined whether a biomarker-based surveillance could be feasible.Case PresentationWe report a unique case of a 26-year-old Caucasian male with recurrent non-muscle invasive bladder tumors occurring at a high frequency and analyzed multiple tumors (maximal pTaG2) and urine samples of this patient. Analysis included FGFR3 mutation detection, FGFR3 and TP53 immunohistochemistry, mircosatellite analysis of markers on chromosomes 8, 9, 10, 11 and 17 and a genome wide single nucleotide polymorphism-array (SNP). All analyzed tumors contained a mutation in FGFR3 and were associated with FGFR3 overexpression. None of the tumors showed overexpression of TP53. We found a deletion on chromosome 9 in the primary tumor and this was confirmed by the SNP-array that showed regions of loss on chromosome 9. Detection of all recurrences was possible by urinary FGFR3 mutation analysis.ConclusionsOur findings would suggest that the BC disease course is determined by not only a patient's age, but also by the molecular characteristics of a tumor. This young patient contained typical genetic changes found in tumors of older patients and implies a clinical disease course comparable to older patients. We demonstrate that FGFR3 mutation analysis on voided urine is a simple non-invasive method and could serve as a feasible follow-up approach for this young patient presenting with an FGFR3 mutant tumor.

Young Age as a Prognostic Factor for Operable Breast Cancer: Significance of Molecular Subtype in Recurrence-Free Survival.

Abstract Background: Breast cancer is uncommon in young women. Biology of the disease in this age group is poorly understood and the prognostic significance of young age at diagnosis remains controversial. We investigated the clinicopathological characteristics and outcomes of younger breast cancer patients (≤35 years of age), and assessed the prognostic significance of young age according to molecular subtype.Methods: We analyzed 2,474 primary invasive breast cancer patients who underwent surgery between 2000 and 2005. The younger age group consisted of patients aged ≤35 years. Subtypes were defined by expression of hormone receptor (HR) and HER2: luminal (HR+ irrespective of HER2 status), triple-negative (HR- and HER2-) and HER2 (HR- and HER2+).Results: A total of 229 (9.3%) patients were aged ≤35 years. Breast cancers in this age group were associated with larger size, higher lymph node positivity, higher nuclear and histological grades, and elevated Ki-67 index, compared with tumors in older patients. Younger patients had a greater probability of recurrence than older patients (P<0.001). By multivariate analysis, young age remained a significant predictor of recurrence (hazard ratio, 1.54; 95% confidence interval, 1.15-2.06; P=0.004). When the cancer subtypes were considered, young age was a significant predictor of recurrence in patients with both luminal and HER2 subtypes. In patients with the triple-negative subtype, however, young age was not a predictor of recurrence.Conclusions: Young age (≤35 years) was an independent predictor of recurrence for operable breast cancer patients with the luminal and HER2 subtypes, but not for those with the triple-negative subtype. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4063.

Equal care for the elderly with low-grade gliomas?

Major prognostic factors for adult patients with primary brain tumors of the astrocytic and oligodendroglial series include age, resectability, physical condition, and histopathologic grade.1 With a peak age incidence of 53 years, glioblastoma multiforme (GBM) is relatively common among older patients, and compared to their younger counterparts, the tumors of older patients are more likely to have genetic changes consistent with “primary” GBM rather than low-grade glioma evolving to GBM; furthermore, older patients have a substantially worse prognosis.2,3 Due to their shorter survival, older patients are often treated with abbreviated courses of radiation therapy. Concurrent and adjuvant chemotherapy with temozolomide confers little benefit in older patients when added to irradiation.4 On the brighter side, the VEGF inhibitor bevacizumab appears to be more active against the GBMs of older patents.5 Low-grade (grade II/IV) gliomas (LGG) have a peak age incidence of 34 years, and due to their relative rarity in older patients, our …

Prognosis and hormone receptor status in older and younger patients with advanced-stage papillary serous ovarian carcinoma

Objective Prior studies have suggested that patients diagnosed with ovarian cancer at an older age have worse outcomes. However, few studies have examined whether differing patterns of protein expression in tumors in older patients correlate with this poorer prognosis. We investigated the correlation of age with prognosis and the significance of hormone receptor status in younger versus older patients through construction of a clinically-annotated high-density tissue microarray (HTMA) composed of stage III and IV papillary serous ovarian cancer cases. Methods Two cohorts of patients (age ≥ 65 and ≤ 55 at diagnosis) were identified retrospectively from ovarian carcinoma pathology cases reviewed at our institution between 1999 and 2005. An HTMA was constructed from 148 eligible cases, and clinical data were abstracted through chart and database review. Results No difference in survival was observed between younger and older patients. Patients ≥ 70 years had decreased survival on univariate, but not multivariate, analysis. ER was significantly more likely ( p = 0.01) and PR significantly less likely ( p = 0.02) to be expressed in older patients. Neither ER nor PR independently correlated with survival in the overall study population. Conclusions Patients with advanced-stage papillary serous ovarian cancer ≥ 65 years of age at diagnosis have a similar survival as patients ≤ 55 years. Hormone receptor status differs significantly between the two age groups, and in the younger patient cohort, there is a trend towards longer overall survival for ER/PR positive tumors. These results suggest that ovarian cancer in younger patients differs biologically from that in older patients.

Cryoablation for Small Renal Tumors in Older Patients

Incidental detection of solid renal masses during abdominal imaging is increasing in older patients (JW Nov 30 2006). Although these masses often are malignant histologically, many are indolent clinically. A therapeutic option for patients who are poor surgical candidates is cryoablation, in which cryoprobes are inserted …

Relationship between Age at Diagnosis and Clinicopathologic Features of Renal Cell Carcinoma

ObjectivesTo analyse the influence of age at diagnosis on tumour characteristics and cancer-specific survival in renal cell carcinoma (RCC). MethodsData on age, tumour characteristics, and survival for 4774 patients from 12 European RCC databases were recorded. Patients were divided into four groups according to age at diagnosis: ≤40, >40 and <60, ≥60 and <80, and ≥80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific survival. The groups were compared for usual clinical and pathologic variables, and cancer-specific survival. ResultsThe four groups accounted for 288 (6%), 1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman grade (p<0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients ≤40 yr were more likely to have papillary or chromophobe RCCs and less likely to have clear-cell RCCs. No significant difference was found among groups for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis age category remained an independent prognostic parameter (p<0.001). ConclusionsRenal tumours diagnosed in younger age are characterized by lower tumour stages and grades as well as favourable histologic patterns compared with tumours in older patients. Basic research is required for explaining such a relationship between age, tumour aggressiveness, and therefore tumour biology.

Wilms' tumor arising within a mediastinal teratoma

The majority of Wilms' tumors present in young children as an intraabdominal mass of renal origin. The use of multimodal treatment protocols according to internationally recognized treatment guidelines has resulted in extremely high cure rates even in the setting of advanced disease. By comparison, Wilms' tumors in older patients or Wilms' tumors located entirely outside the kidney are extremely rare. Because of the rarity of these tumors and the lack of established treatment guidelines specific to these lesions, older patients with atypical Wilms' tumors are at risk for under treatment and poorer outcomes. We report the case of an 18-year-old man with a Wilms' tumor arising within a mediastinal teratoma and discuss the management of this extremely rare lesion.

Clinicopathologic and genetic characteristics of gastric cancer in young male and female patients

The pathways of gastric cancer in young patients (40 years of age or younger) have not yet been determined. We therefore examined clinicopathologically and genetically 68 gastric cancers in young patients and 66 tumors in older patients (41 years of age or older). Mutations in B-raf and K-ras were identified by PCR-SSCP following sequencing. Microsatellite instability (MSI) and hMLH3 mutations were also examined. Histopathologically, diffuse-type gastric cancer and cancer in the whole of the stomach were found significantly more often in young patients than in older patients (21% vs. 2%, P = 0.0006, and 77% vs. 32%, P < 0.0001, respectively). Genetically, MSI and hMLH3 mutations were found significantly more often in tumors in young patients than in tumors in older patients (15% vs. 4%, P = 0.040, and 9% vs. 0%, P = 0.036, respectively). Tumors in young female patients were found significantly less often in the lower-third of the stomach and showed a significantly greater frequency of MSI, compared to tumors in young male patients (33% vs. 9%, P = 0.046, 5% vs. 30%, P = 0.010, respectively). These results suggest that the pathways of gastric carcinogenesis differ between young patients and older patients, and that the pathways differ between the sexes in young patients.

Apoptosis and proliferation related-proteins in breast carcinoma with neoadjuvant chemotherapy

838 Background: Apoptosis and proliferation deregulation plays a role in tumor pathogenesis and progression, and apparently in response to treatment. We studied whether the expression of proteins involved in these mechanisms can identify a subset of breast carcinoma (BC) patients who will respond to neoadjuvant chemotherapy (NACT). Methods: We selected 99 core needle biopsies (CNB) and the corresponding resection specimens from BC patients in NACT. Clinical response (CR) based on tumor size was classified as complete (100%), partial incomplete (>50%), minor (<50%) or progression. Tumor cellularity was assessed in CNB sections and specimens as the percentage invasive cells. Specimens were classified by a five-point grading system. Staining for Bcl2, Bad (pBad Ser136), cleaved Caspase-3, p53, Her2/neu and Ki67 was performed in CNB. All antibodies were scored based on the proportion except for pBad that was considered as negative (no/faint) or positive (moderate/strong). Results were correlated with CR, pathologic response (PR) and clinico-pathological factors. Results: Patients median age was 49 years (range 25–80). Median initial tumor size was 5.5 cm (range 1.5–12) and after treatment 3.2 cm (range 0–15) (p=0.02). 88% were of ductal type, 12% lobular and 63% grade 3. Overexpression of Bcl2 (>50%) or p53 (>20%) was observed in 51% and 41%, respectively; pBad was present in 44% tumors; activated caspase-3 (>50%) in 17% and Ki67 (>30%) in 27%. Complete CR was seen in 37% and PR and 17% (p=0.002). Tumor cellularity decreased from a median of 30% to 5% and 30% showed >90% reduction of the clinical size (p<0.000). Her2/neu was positive in tumors of older patients (p=0.02) with high Ki-67 (p=0.04) and predicted tumor reduction (p=0.03). Ki67 and p53 overexpression was seen in grade 3, with low Bcl2 (p30% (p=0.02) and as a trend with pBad (p=0.09). The grade of PR correlated with pathological size, cytological changes and lymph-node status (p<0.04), and as a trend with Bcl2 (p=0.07), Her2/neu (p=0.09) and Ki67 (p=0.11). Conclusions: In BC following NACT, Ki67 correlates with CR. The observed trend towards improved PR depending on the levels of Bcl-2, Her2/neu and Ki67 supports the idea that they may have predictive value. No significant financial relationships to disclose.

Immunohistochemical Expression of Bcl-2, Ki-67, and p21 in Patients with Papillary Thyroid Cancer

Papillary thyroid cancer (PTC) is a slow-growing tumor with a favorable outcome. Still, some low-risk patients develop local or distant metastases and eventually die from their disease. Many molecular markers are involved in proliferation and apoptosis, including Bcl-2, Ki-67, and p21. Because age over 45 is the most important determinant of a poor survival, we analyzed whether the expression of these tumor proliferation markers differs between young and older PTC patients. Our study comprised 108 PTC patients retrospectively selected by age, i.e. those younger than 35 or older than 55 at diagnosis. Formalin-fixed, paraffin-embedded archival tissue blocks were analyzed for Bcl-2, Ki-67, and p21 protein expression by immunohistochemistry. We showed that expression of Ki-67 increases significantly with age, indicating that tumors in older patients may grow faster. This higher proliferative activity may explain the worse prognosis in these patients. Expression of p21 was higher in large tumors and in tumors extending beyond the thyroid capsule. Expression of Bcl-2 did not correlate with clinical parameters.

Microvessel density and clinicopathological characteristics in hepatitis C virus and hepatitis B virus related hepatocellular carcinoma

Aims: To compare intratumorous microvessel density (MVD) and clinicopathological features in two different groups of hepatocellular carcinoma (HCC), namely: hepatitis B virus (HBV) related HCC (B-HCC) and HCV related HCC...

Alteration of E‐cadherin‐mediated adhesion protein is common, but microsatellite instability is uncommon in young age gastric cancers

Gastric adenocarcinoma in young patients has been considered to differ in many ways from gastric carcinoma in older patients. This study was designed to determine the clinicopathological features and molecular mechanisms. Based on 4123 patients of gastric cancer in Seoul National University Hospital, 135 patients (3.3%) were chosen by the age of 30 years or younger. Expression of E-cadherin, beta-catenin, p53 and Epstein-Barr virus (EBV) was analysed using the tissue array method in formalin-fixed paraffin-embedded specimens and microsatellite instability (MSI) was determined. As a control, 320 cases of older patients were compared. Gastric adenocarcinoma of young patients revealed significant female predominance, type IV gross type, proximal location, diffuse type and frequent lymph node metastasis. In-situ hybridization for EBV showed higher positivity in young patients (9/78, 11.5%) than in older ones, but not statistically significant. In EBV+ cases, p53 over-expression was significantly higher in young patients than older patients (P < 0.05). Alteration of E-cadherin or beta-catenin was significantly higher in younger patients than in older patients (P < 0.05). Overall survival was significantly poorer in younger patients than older ones. The frequency of MSI was rare (1.3%, P < 0.05) in young patients compared with older patients (9.3%). These data indicate that gastric adenocarcinoma of young patients has a poor prognosis, possesses aggressive histopathological features, exhibits reduced expression of E-cadherin and beta-catenin, and demonstrates lower MSI than tumours in older patients.

EGFR overexpression and radiation response in glioblastoma multiforme

Purpose: Recent studies have suggested relative radioresistance in glioblastoma multiforme (GM) tumors in older patients, consistent with their shorter survival. Two common molecular genetic abnormalities in GM are age related: epidermal growth factor receptor (EGFR) overexpression in older patients and p53 mutations in younger patients. We tested whether these abnormalities correlated with clinical heterogeneity in GM response to radiation treatment.Methods and Materials: Radiographically assessed radiation response (5-level scale) was correlated with EGFR immunoreactivity, p53 immunoreactivity, and p53 exon 5–8 mutation status in 170 GM patients treated using 2 prospective clinical protocols. Spearman rank correlation and proportional-odds ordinal regression were used for univariate and multivariate analysis.Results: Positive EGFR immunoreactivity predicted poor radiographically assessed radiation response (p = 0.046). Thirty-three percent of tumors with no EGFR immunoreactivity had good radiation responses (>50% reduction in tumor size by CT or MRI), compared to 18% of tumors with intermediate EGFR staining and 9% of tumors with strong staining. There was no significant relationship between p53 immunoreactivity or mutation status and radiation response. Significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age.Conclusion: The observed relative radioresistance of some GMs is associated with overexpression of EGFR.

Relationship between age, histological type, and size of ovarian tumors

Objective: To clarify the relationship between age, histological type, and size of ovarian tumors. Method: A review was made of 1648 cases of histopathologically diagnosed ovarian tumors and tumor-like lesions, and information on the age of the patients and size of the tumor was obtained. Statistical analysis was performed using Kruskal–Wallis tests or Mann–Whitney U-tests. Results: There were 840 (51%) cases of benign tumors, 73 (4%) cases of tumors of low malignant potential (LMP), 268 (16%) cases of malignant tumors and 467 (28%) cases of tumor-like lesions. The age of the patients was significantly different among tumor-like lesions (34.6±8.1 years), benign tumors (39.8±16.4 years), LMP tumors (45.2±18.3 years) and malignant tumors (51.9±13.0 years) ( P<0.0001). The maximum diameter of the tumors was significantly different among tumor-like lesions (7.1±3.3 cm), benign tumors (10.9±5.6 cm), malignant tumors (13.6±6.5 cm) and LMP tumors (18.5±6.8 cm) ( P<0.0001). Conclusion: The distribution of tumor histological type (tumor-like lesions, benign, LMP and malignant) was correlated against patient age and lesion diameter, with tumors in older patients or larger tumors more likely to be malignant.

Radical resection of periampullary tumors in the elderly: evaluation of long-term results.

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65-87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 +/- 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients > or =75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.

Radiographic and histologic patterns of calcification in chondromyxoid fibroma.

To evaluate the frequency of radiologic and histologic manifestations of matrix calcification in chondromyxoid fibromas. Forty-four cases of chondromyxoid fibroma were reviewed. The age range of the patients was 3-70 years (average 29 years). Calcification was found microscopically in 15 cases (34.1%). In five cases (12.5%) it was demonstrated on plain films or CT. The age range of the patients with microscopic evidence of calcified matrix was 14-70 years (mean 46 years), while that of the patients with non-calcified lesions was 3-59 years (average 21 years). All but two of the patients who showed microscopic calcification in the tumors were over 40 years of age. Four microscopic patterns of calcification were observed: coarse granular, circumscribed, trabecular, and "chicken-wire." Calcification in chondromyxoid fibroma was found more frequently than in previously reported studies. There was a tendency for this phenomenon to occur in the tumors of older patients, particularly those over 40 years old, and in chondromyxoid fibromas situated in flat bones, including ribs.

RADIOTHERAPY IN THE TREATMENT OF DERMATOLOGIC MALIGNANCIES

Although advances in surgical techniques, particularly micrographic surgery, have considerably expanded its role in the management of dermatologic malignancies, radiotherapy remains of considerable value. Its use should be considered in particular for the appropriate solid tumors in older patients, for metastatic disease, and for the more radioresponsive tumors including Merkel cell carcinoma, Kaposi's sarcoma, and the cutaneous lymphomas.

Prognostic implications of p53 overexpression in supratentorial astrocytic tumors.

The wild-type p53 gene is thought to play a critical role in tumor suppression and has been shown to reverse the transformed phenotype of tumor cells in vitro. Mutational inactivation of this aspect of p53 activity occurs frequently in many human neoplasms, including astrocytomas, and is thought to represent a critical step in tumor progression. We have found previously that the presence of p53 immunoreactivity was significantly associated with malignant astrocytomas arising in younger patients, although occurring infrequently in tumors in older patients. Given that young age is the most consistent clinical factor predictive of longer survival in patients with astrocytomas, this suggested that p53 protein accumulation might be a molecular predictor of enhanced survival. To test this hypothesis, we retrospectively studied the association of p53 overexpression with survival in 149 patients with astrocytomas, using univariate and multivariate analysis to determine its value in predicting survival. Although our analysis reaffirmed the strong association between young age and increased survival, we were unable to demonstrate any difference in survival between patients with Grade III and IV tumors with p53 immunoreactivity compared with those without. Presumably, once a tumor has progressed to high grade, the relative importance of p53 status as a predictor of survival is low, probably because of the large number of accumulated genetic alterations associated with malignant tumors. In contrast, the presence of p53 overexpression in Grade II astrocytomas seemed from survival curves to indicate shorter survival compared with patients who had no p53 immunoreactivity. However, this variable did not quite reach statistical significance (P = 0.08) as an independent predictive variable in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac fibroma: Clinicopathologic correlates and surgical treatment

The clinicopathologic findings of 23 patients with cardiac fibroma are presented. The mean patient age was 13 years, with a range of 1 day to 56 years. The presenting symptoms included heart failure, arrhythmias, sudden death, cyanosis, and chest pain. Some patients had no symptoms, and one patient had Gorlin's syndrome. Echocardiography and magnetic resonance imaging were very sensitive in diagnosis. Nineteen patients underwent tumor resection or biopsy, and four tumors were diagnosed at cardiac transplantation or autopsy on explanted hearts. In five surgical cases, complex operations were necessary, including pericardial or synthetic patches, valve replacement, or coronary artery grafting. Two operative deaths occurred in patients with surgical resections and four operative deaths in patients who at the time of the operation were deemed to have inoperable disease and only biopsy was performed. All deaths but one were in patients younger than 2 years of age. Four patients with subtotal resections did well after the operation. Dense collagen was more frequent in tumors in older patients. We conclude that fibromas are congenital tumors that are frequently discovered in adolescents and adults. Surgical treatment is generally successful, and imaging techniques are helpful in preoperative assessment.

Wilms Tumor in Three Patients With Bloom Syndrome

Bloom syndrome is a rare autosomal recessive disease character ized by growth failure, sun-sensitive facial telang!ectasia, and defective immunity. Cytogenetically, the syndrome is defined by a high frequency of sister chromatid exchanges? Increased risk of cancer has been recognized as a feature of Bloom syndrome since 1965. 2 In children with this syndrome, acute leukemia and lymphoma have been the predominant cancers, wi th solid tumors in older patients. W e now report three unrela ted children with Bloom syndrome in whom Wilms tumor was diagnosed independent ly at three Canad ian centers from 1981 to 1985. The development of Wilms tumor in three pat ients with Bloom syndrome among just more than 100 pat ients worldwide suggests tha t the incidence of this tumor in these pat ients is markedly increased.