Stage II-IV Patients Research Articles

Prognostic significance of tumor suppressor gene maspin in pulmonary adenocarcinoma

7162 Background Maspin is a unique member of the serine protease inhibitor family with tumor suppressive potential in breast and prostate cancer. Recent studies have shown that loss of maspin expression correlates with progression and metastasis of tumors and poor prognoses for patients with several types of cancers. Paradoxically, maspin expression has been reported in ovarian and pancreatic cancers. However, the presence of maspin expression in pulmonary cancers has not been evaluated. In this study, we evaluated maspin expression in pulmonary adenocarcinoma in relation to a number of clinicopathological features. MethodsMaspin expression was examined immunohistochemically in a series of 78 pulmonary adenocarcinomas. ResultsThirty-seven (47%) showed distinct maspin expression (maspin-positive group) and 41 (53%) did not (maspin-negative group). In the surrounding pulmonary tissues, alveolar epithelial cells lacked maspin expression, but maspin staining was usually present in bronchial basal cells and occasionally present in surface bronchial epithelial cells. Maspin expression was not associated significantly with most clinicopathological variables including sex, age, tumor size, primary tumor, lymph node metastasis, visceral pleural invasion, pulmonary metastasis, stage grouping and p53 expression. However, the maspin-positive group had a better 5-year survival rate (62%) than did the negative group (42%). The difference in the 5-year survival rate was more significant in stage II-IV patients (maspin-positive group, 53%; -negative group, 16%, p = 0.049). Conclusions Our data indicate that maspin has prognostic significance for pulmonary adenocarcinoma. A better understanding of the role of maspin in tumor suppression may be helpful for development of novel chemotherapies for patients with this deadly tumor. No significant financial relationships to disclose.

Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion.

The natural history of serous borderline tumors (SBTs) of the ovary varies considerably. A group of investigators have proposed that a small subset of SBTs with a micropapillary architecture and an allegedly higher incidence of invasive peritoneal implants should be designated "micropapillary serous carcinomas." Based on the overall favorable prognosis of the nonmicropapillary SBTs, these investigators have recommended abandoning the borderline category of serous tumors, restricting them to benign (benign and typical SBTs) and malignant types; other investigators, however, are in favor of retaining the original grouping, designating borderline tumors with a micropapillary pattern as such instead of designating them carcinomas. We have reviewed the clinicopathologic records of 137 patients with ovarian SBTs and obtained follow-up information on 106 of them ranging from 1 to 18 years (mean 7 years). Of the 21 patients with stage I tumors who had conservative surgical treatment, only two (9.5%) were subsequently found to have tumor in the contralateral ovary. Both were successfully managed by reoperation alone. Forty-five stage I patients had procedures that included bilateral oophorectomy, and two of them (4.4%) had a pelvic recurrence, which was fatal in one patient (whose tumor had been understaged) and occurred on multiple occasions in the other patient, finally transforming into invasive carcinoma; that patient survived. Of the 45 stage II-IV patients, only the six (13%) with invasive implants had an unfavorable outcome: three died of tumor (from 7 to 9.3 years), and the other three were alive with progressive disease from 5 to 10 years. Solid epithelial nests or small papillae surrounded by clefts and micropapillary architecture were found more often in invasive than in noninvasive implants. However, the only feature specifically associated with a poor outcome was obvious destructive invasion of the underlying tissue. Among the 137 SBTs, we identified 18 cases of serous borderline tumors with a micropapillary pattern (SBT-MP) (so-called "micropapillary carcinoma") and 20 cases of SBT with microinvasion (SBT-Minv) (three of which were also micropapillary). We compared the two groups of tumors with the remaining 102 cases of typical SBTs (which lacked micropapillary pattern and microinvasion). Of the 17 patients with SBT-MP and follow-up data, only the one patient with invasive implants had an unfavorable outcome; similarly, of the two patients with SBT-Minv and an unfavorable outcome, one had invasive implants and the other had been incompletely staged. SBTs have a very favorable prognosis, but complete surgical staging and prolonged follow-up are advised because pelvic recurrence and occasionally transformation to invasive carcinoma may occur. Designation of SBTs as "atypical proliferative tumors" is not recommended because it discourages complete surgical staging and follow-up. Advanced stage tumors with noninvasive implants are common, characteristically behave in a benign fashion, and can be safely treated conservatively. The rare SBTs associated with invasive implants are almost always fatal. SBT-MP and SBT-Minv are much closer in their biologic behavior to SBTs than to serous carcinomas. The micropapillary pattern alone does not imply an unfavorable prognosis; only micropapillary tumors associated with invasive implants behave aggressively.

Reverse transcriptase polymerase chain reaction (RT-PCR) detection of melanoma-related transcripts in the peripheral blood and bone marrow of patients with malignant melanoma. What have we learned?

The detection of circulating tumor cells (CTC) and bone marrow micrometastases (BMM) by reverse transcriptase polymerase chain reaction (RT-PCR) may help predict recurrence and survival in malignant melanoma (MM). Since the appearance of the original article by Smith et al. in 1991 (Lancet 338:1227), several groups have attempted the detection of CTC and BMM in MM using RT-PCR for melanocytic specific markers, mainly tyrosinase mRNA. Most studies show that tyrosinase is not present in the PB and BM of control individuals without MM. The PCR positivity rates in MM are extremely variable, ranging from 0% to 100%. There was a correlation between RT-PCR and stage in some but not all of the studies. These disparate findings could in part be explained by differences in RNA extraction and blood separation techniques, to unrecognized contamination leading to false positive results, or differences in patient selection. Despite these discrepancies, we and others have shown that RT-PCR for tyrosinase mRNA in PB is able to predict overall survival (OS) and disease-free survival (DFS) in a statistically significant manner. In AJCC stage II-IV patients rendered surgically free of disease, we found that blood tyrosinase positivity was an independent predictor of OS and DFS. We also found that BM tyrosinase positivity is an independent predictor of DFS in the same group of patients. RT-PCR may help identify subgroups of patients at high risk for early relapse for more aggressive adjuvant therapy. Large prospective studies and interlaboratory quality assurance initiatives are necessary to confirm the accuracy and prognostic value of these RT-PCR assays.

Use of hospital services by breast cancer patients by stage of the disease: implications on the costs of cancer control.

The use of resources for breast cancer during the first five years after diagnosis by different stages of disease was evaluated on the basis of all breast cancer patients (555) diagnosed in the Tampere University hospital district (Finland). All outpatient visits or inpatient-days of these patients in any hospital of the district were recorded and the average costs of hospital-day and of outpatient visit were applied to quantify the total use of resources. During the first five years of follow-up 535 breast cancer patients had 8206 follow-up visits and spent 18472 days in hospital. The stage II-IV patients had more than twice as many outpatient visits and inpatient-days as the stage I patients. The number of hospital-days/patient-year was 2.4-fold for stage II patients and 4.1-fold for stage III-IV patients as compared to stage I patients. The overall use of resources/patient for those with nonlocalized disease was twice as high as the use for stage I patients, while the use of resources/person-year was 2.3-fold for stage II patients and 3.6-fold for stage III-IV as compared to stage I patients. Our study in an unselected patient population during the first five years of follow-up shows that breast cancer patients diagnosed in the early stage (stage I) require far fewer health care resources than if diagnosed in advanced stages. The results can be directly transformed into costs of breast cancer control by stage of breast cancer.

Prognostic value of non-MHC-restricted killer cell activity in lung cancer.

The prognostic value of peripheral blood non-MHC-restricted cytotoxicity against the myeloid leukaemic line K562 in lung cancer patients was studied. At the time of diagnosis and before operation, 57 patients with lung cancer were tested for cytotoxicity and subsequently followed for up to 4 years. In addition, 145 lung cancer patients, 30 patients with non-neoplastic lung diseases and 76 healthy donors were tested for cytotoxicity without the follow-up, in order to correlate the stage of lung cancer and the growth rate of tumours to the level of non-MHC-restricted cytotoxicity. On average, lung cancer patients had similar non-MHC-restricted cytotoxicity to the controls. However, patients with stage II-IV diseases showed an impaired activity, stages III and IV differing significantly from the controls. This result shows that the decline in natural killer (NK) activity is associated with tumour burden. Patients with slowly growing neoplasms had stronger cytotoxic activity than patients with fast or moderately progressing disease. In the follow-up study, the whole material of 57 patients showed only a slight correlation between cytotoxicity and survival: 42% of the patients with strong activity survived for more than 2.5 years, whereas 6% of the patients with weak activity did so. In stage I patients there was no correlation between cytotoxicity and survival, nor was there a correlation in patients with stages II-IV of the disease. Hence, in our group of patients the determination of cytotoxicity preoperatively yielded no prognostic information beyond that already available from staging. However, those stage II-IV patients that survived for 1 year or more after the diagnosis and cytotoxicity tests, showed a significant correlation between cytotoxicity and survival.

Combined modality treatment of cutaneous T cell lymphoma: results of a 6-year follow-up.

Thirty-nine patients with cutaneous T cell lymphoma (CTCL; including mycosis fungoides or the Sezary syndrome) with no previous treatment other than topical therapy or oral corticosteroids, received total skin electron beam irradiation (TSEB) and either sequential or simultaneous systemic chemotherapy. Median follow-up, measured from the time of initiation of therapy to the time of analysis, is in excess of 6 years and extends to 100+ months. Thirteen patients with stage I disease (limited to skin with no adenopathy) received 3,000 rad total skin electron beam irradiation followed by three 2-week courses of daily intravenous (IV) mechlorethamine. Twenty-six patients with advanced disease (stage II-IV) received 2,400 rad of TSEB and simultaneous chemotherapy with two alternating three-drug regimens: vinblastine, doxorubicin, and bleomycin (VAB) alternating with cyclophosphamide, methotrexate, and prednisone (CMP) administered over 54 weeks. The overall response rate was 92% with 16 of 39 patients (41%) achieving a histologically documented complete response (CR). Stage I patients had a significantly increased CR rate (77%) compared with stage II-IV (P less than .01). The overall 6-year survival was 92% for stage I patients and 26% for stage II-IV patients (23%) (P less than .001). Among ten completely responding stage I patients, six remain alive and disease-free in excess of 72 months. The median disease-free survival is 26 months for completely responding stage II-IV patients (P = .04), but none are continuous disease-free survivors after protocol treatment. We conclude that combined modality treatment can be safely administered and produces prolonged disease-free survival in some stage I patients, but not in more advanced stage patients.