Relationship of testosterone, sex hormone binding globulin, and calculated free testosterone to subsequent clinical progress in patients with carcinoma of the prostate treated with bilateral orchidectomy or estrogens.

The concentration in serum of testosterone, sex hormone binding globulin (SHBG), and albumin has been measured, and from these measurements free testosterone has been calculated in 75 patients with carcinoma of the prostate treated with either bilateral orchidectomy, stilbestrol, or estramustine phosphate (Estracyt). After exclusion of 3 noncompliant patients, total testosterone did not differ significantly between treatments, but free testosterone was lower in estrogen-treated patients (5.9 +/- 0.9 (SEM) pmol/l, n = 28) compared with the orchidectomized patients (23 +/- 1.4 pmol/l, n = 44) (P less than 0.001); all of the estrogen-treated patients falling in the lower third of the range of the orchidectomized patients. Free testosterone did not change systematically during several years of treatment and there was no evidence of a rise with clinical deterioration. In the 33 patients with metastatic cancer treated with orchidectomy, the third with the lowest free testosterone or total testosterone showed a better survival over 2 years than the two-thirds with higher free or total testosterone; thereafter, the advantage was lost.

Evaluation of an amplified enzyme-linked immunoassay of placental alkaline phosphatase in testicular cancer.

The levels of serum placental alkaline phosphatase (PLAP) have been examined in 81 male controls, 51 untreated testicular tumours (41 seminomas and ten non-seminomatous testicular tumours) and 34 patients in complete remission (11 seminoma and 23 non-seminoma). Smoking induced a significant rise of serum PLAP in the controls, with a median level of 0.055 U/1 in non-smokers compared to 0.25 U/l in smokers. The levels found in pre-treatment seminoma (median 1.7 U/1) were significantly higher than in untreated teratoma (median 0.7 U/1). Treatment produced a significant fall in seminomas in remission (median 0.07 U/1). The role of PLAP in routine monitoring of seminomas was evaluated in 17 patients studied for 1-4 yr. PLAP shows similar trends to beta HCG but is an independent variable. The main role of PLAP is to help determine that the response to treatment has been satisfactory and that there are no unexpected foci of tumour.

The prognostic significance of acute phase proteins in patients with inoperable squamous cell carcinoma of the bronchus.

In 95 patients with inoperable squamous cell carcinoma of the bronchus, nine potential serum "markers" were analysed for their prognostic significance. Lactate dehydrogenase, alpha 1 HS-glycoprotein, ferritin, carcino-embryonic antigen and immunoglobulin E did not prove to be useful as prognostic indices. The erythrocyte sedimentation rate and the acute phase proteins alpha 1 acid glycoprotein, C-reactive protein and prealbumin were correlated with survival. After taking the performance status and tumour stage into account, C-reactive protein still proved to be a strong prognosticator. The clinical relevance of the acute phase proteins signifying a so-called "biochemical status" next to the "clinical status" is discussed.

Immunoglobulin A, G and E levels in Egyptians with cancer: influence of schistosomiasis.

The main patient series consisted of 415 Egyptians attending the Cairo Cancer Institute and comprising 286 bladder cancer, 97 breast cancer, 14 head and neck cancer and 18 gastrointestinal cancer cases. Also included in the study were 36 patients with active schistosomiasis and 89 health controls. Serum IgA, IgG, IgG subclasses, IgE, Schistosoma and Ascaris-specific IgE (RAST) and the acute-phase protein CRP were measured in all, or sub-sets, of the main patient group. The well-established increase in IgE and IgG levels, and the more recently reported increase in the levels of IgG3 and IgG4 subclasses in patients with schistosomiasis, were also found in bilharzial bladder cancer, indicating that humoral immunity persists in cancer-bearing patients. However, the plasma protein profile in bilharzial bladder cancer is further modified by significant increases in the levels of IgA, IgG, IgG1, IgG2 and CRP when compared to levels in patients with Bilharzia in the absence of neoplastic change. Patients with cancers not associated with parasitic infestation also had significant increases in their serum levels of IgG1, IgG2, IgG, IgE and CRP when compared to healthy Egyptian controls, but 41% of these non-bladder cancer patients showed IgE responses to previous parasitic infestations suggesting that any immunological response to cancer would be on the background of a variable non-specific increase of IgE.

Biochemical aids in the monitoring of patients with ovarian cancer.

A study of possible biochemical markers of tumor recurrence and progression was made in 93 patients with ovarian cancer followed longitudinally for up to 2 years during treatment by moderate or aggressive chemotherapy regimens. A panel of potential indicators was tested; the combination of serum albumin, C-reactive protein, alpha 1-acid glycoprotein, and phosphohexose isomerase levels was found to provide information that is useful as an adjunct to the clinical assessment of patients with advanced disease. However, the system could not detect a small tumor burden. The level of beta 2-microglobulin may have value in those patients whose tumor is associated with an increase of this analyte (77%), but it would appear to reflect a large tumor mass. Serum CEA, carcino-placental alkaline phosphatase, transferrin, and prealbumin were not found to be helpful.

Monitoring of prostatic cancer by an enzyme-linked immunosorbent assay of serum prostatic acid phosphatase.

A longitudinal study of serum prostatic acid phosphatase (sPAP) in 167 cases of carcinoma of the prostate was made using an enzyme-linked immunosorbent assay. The sensitivity of the assay was valuable in accurately exploring the low levels of sPAP achieved after treatment by orchidectomy or oestrogens. For the majority of patients with metastatic disease, treatment resulted in the level of sPAP falling to normal within 3-9 months, but in about half of these patients the level of sPAP had begun to increase again, exponentially, within 2 years. This exponentially rising level of sPAP was well correlated with evidence of progression as indicated by bone scans. The rise of sPAP in M1 disease could not be accounted for by an attenuation of the suppression of testosterone. After hormone manipulation in M0 disease the sPAP generally fell to below 1.5 ng/ml and remained at this level for the duration of the study. In untreated M0 disease there were small fluctuations in the level of sPAP, and it had a higher baseline level. In both treated and untreated patients a rising level of sPAP above normal tended to indicate tumour progression.

Limitations of using pregnancy-associated alpha-2 glycoprotein as a tumour marker.

The development of a new enzyme-linked immunoassay for pregnancy-associated alpha-2 glycoprotein (alpha 2-PAG) has provided an opportunity to reassess the value of this protein as a tumour marker. Serum samples from 800 healthy individuals and patients with various benign and malignant diseases were assayed. There was a very wide range of alpha 2-PAG levels in normal females (1- greater than 100 mg/l), and although the levels found in normal males were lower and better defined, this intrinsic variation between individuals makes a single determination in a tumour-bearing patient meaningless. Also, the levels of alpha 1-PAG in patients with advanced cancer were not significantly different from levels in localized cancer, benign disease or even healthy controls, and furthermore, levels before and after successful cancer treatment did not show a significant change. Our results therefore indicate that alpha 2-PAG is unsuitable for use as a tumour marker as there was no apparent relationship between the levels of alpha 2-PAG and either tumour burden or response to treatment.

Serum protein profiles in carcinoma of the kidney.

The levels of serum acute phase reactant proteins (APRPs) have been examined in untreated kidney carcinoma and during the evolution of metastases. These proteins can provide a warning of the likelihood of extensive local or metastatic spread at first presentation. The levels of APRPs rise with increasing tumour burden but the system is insensitive to small tumour burdens. beta 2-Microglobulin levels do not contribute additional information. Serum phosphohexose isomerase tends to be elevated when there is a large tumour burden but its change does not accurately mirror the rate of expansion of the tumour. The APRPs and phosphohexose isomerase are useful in alerting the clinician to the probability of metastases or large local masses in kidney cancer, but have a limited use in monitoring.