Positive urinary cytology in patients with lung cancer in the absence of obvious urine tract metastases.
OBJECTIVE
To study the phenomenon of positive urine cytology in patients with lung cancer in the absence of obvious urothelial metastases.


METHODS
150 patients with small (SCLC) and non-small cell lung cancer (NSCLC) of all stages and 3 control groups were prospectively studied. Immunocytochemical study (cytokeratins 7-20, TTF1) in all positive urine specimens and chemokine profile (CXCR4, CCL21) study of the primary tumor in selected positive patients was performed. In experimental study, C57Bl/6 BALB/C mice injected with LLC lung and 4T1 mammary cancer cells were used for the detection of positive urine cytology.


RESULTS
11% of patients with NSCLC, 7% of patients with SCLC and none of the control group had positive urine cytology. In NSCLC, metastatic disease and high tumor burden positively correlated (p=0.01 and 0.03 respectively) with the phenomenon. In SCLC, correlation with extensive disease and multiple metastatic sites (p=0.02 and 0.04 respectively) was found. No correlation was found in either group with: age, gender, histology, performance status, line of chemotherapy, previous platinum-based chemotherapy, adrenal metastases, renal function, abnormal urinary sediment, response to chemotherapy and overall survival (p=0.9). Distinctive chemokine expression was identified in positive patients studied and was not observed in negative patients (×2 p=0.008). In the experimental study, only the LLC lung cancer cells were detected in the urine cytology of mice.


CONCLUSIONS
This phenomenon, carrying undefined pathophysiological mechanisms, seems to characterize only patients with metastatic/extensive disease and high tumor burden. Further studies are needed to validate our preliminary chemokine expression results.
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
E
E
Voulgaris
G
G
Pentheroudakis
L
L
Pappa
M
M
Bafa
A
A
Goussia
P
P
Dalezis
C
C
Tsombanidou
G
G
Geromichalos
A
A
Papageorgiou
M
M
Koutsilieris
V
V
Malamou-Mitsi
N
N
Pavlidis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000652:urine; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000652:urine*; D016022:Case-Control Studies; D054421:Chemokine CCL21 / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000652:urine*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000652:urine; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D019718:Receptors, CXCR4 / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000652:urine*; D014183:Transplantation, Heterologous; D014571:Urologic Neoplasms / Q000556:secondary
C515478:CCL21 protein, human; C527276:CXCR4 protein, human; D054421:Chemokine CCL21; D019718:Receptors, CXCR4