The prognostic significance of DNA content in carcinoma of the rectum and rectosigmoid

Using cytofluorometric single-cell DNA analysis, the pattern of nuclear DNA content was determined in preoperative biopsies from 166 unselected primary adenocarcinomas of the rectum or rectosigmoid. The pattern was aneuploid (AN) in 125 (75%) of the tumours, was aneuploid (AN) in 125 (75%) of the tumours, near-diploid with aneuploid cells (ND-anc) in 26 (16%) and near-diploid (ND) in 15 (9%). The DNA content was not related to tumour stage or degree of differentiation. The clinical course tended to be more favourable in patients with ND tumour than in those with AN or ND-anc pattern. The nuclear DNA content in rectal carcinoma thus can be estimated in preoperative biopsies, and the pattern may serve as a prognostic parameter.     

Prognostic significance of nuclear DNA content in phaeochromocytoma

Nuclear DNA content of 27 phaeochromocytomas was measured by image analysis of thin sections and monolayer smears of nuclei extracted from thick sections (cytospins) using archival paraffin-embedded tissue blocks. Recurrence was assessed on the basis of clinical follow-up or urinary catecholamine levels. The mean follow-up was 5.0 years, with a range of 4 months to 15 years. Although it is not possible to differentiate accurately malignant tumours using DNA analysis, prediction of benign tumours is possible. Using thin sections, all tumours were benign when the percentage of cells with a DNA content of 2.5 c (2 c = diploid) was less than 40% and the DNA content of 5 c was less than 4%. Using the cytospin preparation, all diploid tumours were benign. Thus, patients with diploid tumours may be saved intensive long-term follow-up. Aneuploid and tetraploid tumours, however, continue to require careful lifelong follow-up.     

Flow cytometric analysis in non-small-cell bronchial carcinoma and its prognostic significance]

Tumor and lymph node infiltration, and the DNA-ploidy status of a tumor contain prognostic information in addition to the information obtained by histological examination of surgical samples. Specimens from 112 patients with non-small-cell lung carcinoma obtained immediately after surgery were investigated by means of flow cytometry. DNA-aneuploidy was found in 43% of the primary tumors. Independent from tumor stage, patients with DNA-euploid tumors lived significantly longer (p less than 0.01) than with DNA-aneuploid carcinomas. In 29 cases the DNA-ploidy status of the primary tumor (PTU) could be compared with that of the N2 lymph node metastases (LM). 7 samples revealed a change from DNA aneuploidy in the PTU to DNA-euploidy in the LM. Patients with DNA-euploid PTU and DNA-euploid LM lived significantly longer than patients with DNA-aneuploid PTU/DNA-euploid LM, and patients with DNA-aneuploid PTU/DNA-aneuploid LM. In case of lymph node infiltration only the simultaneous measurement of DNA ploidy of PTU and LM offers an accurate prognostic evaluation. Local tumor recurrence exhibited stability of DNA ploidy, showing DNA euploidy in 12 out of 13 PTU and their corresponding recurrent tumor. Thus, the DNA-ploidy status offers additional prognostic informations which is useful for an extended tumor classification.     

胰腺癌细胞DNA倍型及临床意义的评价

目的了解胰腺癌细胞DNA倍型及临床意义。方法68例胰腺癌组织标本,行Feulgen染色,应用全自动图像分析仪测定癌细胞DNA含量及倍型。结果本组2倍体／近2倍体（2C）率及异倍体（AN）率分别为26.5％及73．5％。2C肿瘤比AN有较高的手术切除率,较好的预后（P＜0．05）,手术时实测2C肿瘤体积小,临床分期早。DNA倍型与病理分级无关（P＞0．05）,而与临床分期、肿瘤大小相关（P＜0．01）。结论胰腺癌细胞异倍体率高,临床上表现为恶性程度高,手术切除率低,预后差。     

Relationship between the nuclear DNA content and the prognosis in squamous cell carcinoma of the lung

Analysis of the nuclear DNA content from paraffin-embedded specimens using flow cytometry was performed on 86 patients in squamous cell carcinoma of the lung. There were no relationships between the site of tumor origin and the nuclear DNA content or the survival of the patients. The frequency of DNA aneuploidy was 74.4% among tumors, and it significantly (p less than 0.05) increased with advanced stage. The patients with DNA aneuploidy were significantly (p less than 0.01) less favorable prognosed than those with DNA diploidy. Similar results were demonstrated in patients of absolute or relative curative resections. These results indicate that DNA aneuploidy is of higher grade malignant intensity than DNA diploidy in squamous cell carcinoma of the lung. In patients with absolute or relative curative resection, DNA aneuploid tumors occurred much more often in distant metastasis. In conclusion, there were no relationships between the site of tumor origin and the biological features or the prognosis of patients in squamous carcinoma of the lung. DNA ploidy pattern is related to relapse and prognosis of the tumors. If the DNA ploidy pattern of patients on whom absolute curative resection was performed is DNA aneuploidy, adjuvant therapy should be strongly performed and carefully followed up as long as possible.     

Prognostic value of nuclear DNA content in papillary thyroid carcinoma

The prognostic value of nuclear DNA content in papillary thyroid carcinoma was studied retrospectively in 90 patients. Eighty survived for at least 10 years, and 10 died, of papillary thyroid carcinoma, between 6 months and 12 years after diagnosis. Clinical data as well as morphological tumor characteristics were examined. DNA measurements in morphologically identified single tumor cells were performed either on fine-needle aspiration material or on histologic sections. The tumors of the survivors were composed of cells with a DNA content comparable to that of normal cells, whereas the tumors of the non-survivors had significantly higher DNA values. The data suggest that DNA measurements in papillary thyroid carcinoma offer a valuable adjunct to standard clinical and microscopic analysis.

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Resumen El análisis del contenido de DNA en carcinoma prostático, carcinoma mamario y condrosarcoma ha sido demostrado como una mejor guía de pronóstico que los exámenes clínicos y microscópicos convencionales. El propósito de este estudio fue el de evaluar si la determinación del contenido de DNA puede significar un parámetro confiable de pronóstico en pacientes con carcinoma papilar de tiroides.El valor pronóstico del contenido nuclear de DNA en el carcinoma papilar fue estudiado retrospectivamente en 90 pacientes. Ochenta sobrevivieron por no menos de 10 años, y 10 fallecieron de carcinoma papilar entre 6 meses y 12 años después de efectuado el diagnóstico.Los datos clínicos y las características morfológicas del tumor fueron analizados. Las determinaciones de DNA en células únicas morfológicamente identificadas fueron hechas sobre material de aspiración con aguja fina o sobre secciones histológicas. Los tumores de los supervivientes aparecieron compuestos por células con un contenido de DNA comparable al de las células normales, en tanto que los tumores de los pacientes que no sobrevivieron presentaron valores de DNA considerablemente más altos. Estos datos sugieren que las determinaciones de DNA en el carcinoma papilar significan un valioso parámetro de pronóstico adyuvante del análisis clínico y microscópico ordinario, puesto que existe una correlación entre la supervivencia y el contenido de DNA de las células tumorales. La hemitiroidectomía puede ser una forma adecuada de tratamiento en pacientes con tumor unilateral y medición de DNA que indique un pronóstico favorable, en tanto que los pacientes, aún aquellos con un tumor muy pequeño, en quienes las determinaciones de DNA indiquen un pronóstico pobre, pueden exigir una forma más agresiva de tratamiento.

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Résumé La valeur pronostique de l'ADN (DNA) nucléaire en cas de cancer papillaire de la thyroïde a été étudiée chez 90 malades. Quatre-vingts des opérés ont survécu plus de 10 ans mais 10 moururent entre 6 mois et 12 ans après le diagnostic. Les données cliniques aussi bien que les caractères histologiques des lésions furent étudiés. La mesure de l'ADN (DNA) sur les cellules tumorales fut pratiquée soit après biopsie aspiration à l'aiguille fine, soit sur la coupe histologique. Les tumeurs des malades qui survécurent étaient constituées par des cellules dont le taux d'ADN (DNA) était comparable à celui des cellules normales, alors que les cellules des malades qui mouraient présentaient un taux d'ADN (DNA) significativement plus élevé.Cette étude suggère que la mesure de l'ADN (DNA) en présence d'un cancer papillaire de la thyroïde constitue un appoint utile aux données classiques de la clinique et de l'histologie.

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Presented at the International Association of Endocrine Surgeons at Hamburg, September 1983.

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Supported by the Cancer Society in Stockholm grant no. 83:24 and by the Swedish Cancer Society grant no. 83:198     

Clinical significance of measurement of nuclear DNA content in breast cancer

Nuclear DNA content measured by a cytofluorometric method was investigated to evaluate its clinical significance in 73 cases with breast cancer which had extended radical mastectomy. Many cases of D type (diploid type) which had a prominent peak at the 2c region (control DNA content of lymphocytes) were safe indications for modified radical mastectomy. Bone recurrence was significantly more frequent in D type than in N type (non-diploid type) which did not have a prominent peak at the 2c region. Because D type had high positive rate of hormone receptors, endocrine therapy might be effective for many cases. Local or lung recurrence was more common in cases with N type which had a significant low cumulative survival rate compared with D type and especially N type 4c-3 of which over 4c cells more than 30% had the poorest prognosis. Therefore, multidisciplinary treatment composed of extended operation, radiation and chemotherapy was necessary to improve the prognosis of breast cancer patients with N type 4c-3. It was concluded that the measurement of nuclear DNA content in breast cancer might be useful for decision of therapy suitable for each case based on malignancy grading.     

Prognostic value of nuclear DNA content in medullary thyroid carcinoma

The prognostic value of nuclear DNA content in medullary thyroid carcinoma was studied in 36 patients. Eleven patients are still living 13–35 years after diagnosis. Twenty-five patients died of medullary thyroid carcinoma between 10 months and 23 years following diagnosis. DNA measurements in morphologically identified single tumor cells were performed either on fine-needle aspiration biopsy material or on histologic sections from the primary tumor. Metastases or local recurrences were also examined in 18 cases. In the survivors, the majority of tumors exhibited cells with DNA amounts approximating the normal diploid value, whereas the tumors of the nonsurvivors had significantly higher DNA values. The primary tumors and their metastases or local recurrences exhibited in all cases essentially similar DNA content. The data suggest that DNA measurements in medullary thyroid carcinoma contribute valuable prognostic information that adds to standard clinical and morphological parameters.

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Resumen Los análisis del contenido nuclear de DNA de las células tumorales en pacientes con carcinoma prostático, carcinoma mamario y condrosarcoma ha demostrado ser un mejor indicador de pronóstico que los exámenes histopatológicos convencionales. Recientemente también se han realizado estudios de DNA en células tumorales de pacientes con carcinoma papilar de tiroides y tumores foliculares de tiroides. El contenido de DNA de las células tumorales se correlaciona bien con la evolución clínica. Las células tumorales de aquellos pacientes que sobrevivieron por no menos de 10 años frecuentemente exhibieron un contenido de DNA comparable al de las células normales, en tanto que los pacientes que murieron por carcinoma tiroideo exhibieron células con valores elevados del DNA, claramente diferentes de los de las células normales.El valor pronóstico del contenido nuclear de DNA en carcinoma medular de tiroides fue estudiado en 36 pacientes. Once pacientes viven entre 13 y 35 años después de realizado el diagnóstico. Veinticinco pacientes murieron de carcinoma medular de tiroides entre 10 meses y 23 años después del diagnóstico. Las mediciones de DNA en células tumorales aisladas, morfológicamente identificadas, fueron realizadas bien en material obtenido por aspiración biopsia con aguja fina o en secciones histológicas del tumor primario. Metástasis o recurrencias locales también fueron examinadas en 18 casos. En los sobrevivientes la mayoría de los tumores exhibió células con contenidos de DNA generalmente alrededor del valor diploide normal, en tanto que los tumores de los pacientes que murieron tenían valores de DNA significativamente más altos. Los tumores primarios y sus metástasis o recurrencias locales exhibieron, en todos los casos, esencialmente similares contenidos de DNA. Estos datos sugieren que las determinaciones de DNA en el carcinoma medular de tiroides contribuye una información valiosa desde el punto de vista pronóstico, adicional a los parámetros clínicos y morfológicos usuales.

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Résumé La valeur pronostique de l'ADN nucléaire du cancer thyroidien médullaire a été étudiée chez 36 males. Onze malades sont encore en vie de 13 à 35 ans après que le diagnostic ait été porté, vingt-cinq malades sont décédés de 10 mois à 23 ans après que le cancer ait été reconnu. Le dosage de l'ADN au niveau des cellules néoplasiques a été porté sur le spécimen recueilli par la biopsie aspiration ou la pièce opératoire. Il a été également effectué dans 18 cas de métastases ou de récidives locales du cancer. Chez les survivants le taux d'ADN au niveau des cellules diploides était voisin de la normale alors qu'il était significativement plus élevé chez les opérés qui sont décédés. Les tumeurs primitives, les métastases, les récidives avaient dans tous les cas un taux identique d'ADN. Ces données suggèrent que le dosage de l'ADN cellulaire dans les cas de cancer de type médullaire possède une valeur pronostique qui s'ajoute à celle des paramètres cliniques et morphologiques.

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Supported by The Cancer Society in Stockholm and by The Swedish Cancer Society.     

Prognostic significance of the DNA content in renal cell carcinoma

The DNA content in renal cell carcinoma as an indicator of prognosis was studied retrospectively in 55 patients without distant metastases at operation. Two groups of patients were selected, differing with respect to survival. Thirty-three patients survived for at least 10 years and 22 succumbed to the disease within four years. DNA measurements in morphologically identified tumor cells were performed in histological sections by single cell cytophotometry. The tumor cells of the surviving patients had a DNA content comparable to that of normal cells. A diploid/near diploid DNA content was the dominant feature in 32 of these 33 tumors. The remaining patient had a tumor with a tetraploid/near tetraploid DNA value. In contrast, all tumors from the non-surviving patients had abnormally increased DNA content, indicating a high degree of aneuploidy in these tumors. The results suggest that DNA content may be superior to other clinical and microscopical parameters as a prognostic indicator.     

The prognostic significance of DNA ploidy for neuroblastoma

Flow cytometric DNA analysis was performed on 45 neuroblastomas in order to evaluate the prognostic significance of DNA ploidy. The DNA ploidy was diploid in 14 and aneuploid in 31 neuroblastomas and did not correlate with the conventional prognostic variables such as age, Evans' stage, or the primary site of the tumor. The survival of 31 patients with aneuploid tumors was comparable to that of 14 patients with diploid tumors. On the other hand, DNA aneuploidy was associated with a decreased long-term survival in 21 patients older than 24 months of age at the time of operation, and in 27 patients with advanced disease at Evans' stage III or IV. These results suggest that more intensive and longer-term postoperative chemotherapy is necessary for neuroblastoma patients older than 24 months of age, or for those with advanced disease if they have aneuploid tumors.     

Flow cytometric analysis of the nuclear DNA content of hepatocellular carcinoma

The nuclear DNA content of 77 resected specimens from 65 cases of hepatocellular carcinoma (HCC) was measured by means of flow cytometry. The DNA index (DI) was calculated and the correlation between the DNA ploidy pattern and clinicopathological findings was studied. In the cases of HCC with a diameter of less than 5 cm, the 3-year survival rate of the aneuploid cases was 44.5 per cent, which was significantly lower the 91.4 per cent of the diploid cases (p<0.001). Serum AFP levels were over 1000 ng/ml in 46.4 per cent of the aneuploid tumors and 18.5 per cent of the diploid tumors (p<0.05). The DI’s were investigated in several sites of the same tumor and no difference was seen among the different sites in 16 out of 17 tumors. From 8 recurrent cases out of 12 who underwent a second resection, seven did not show any significant differences in DI from their primary tumor. On the other hand, four cases of second primary tumors showed different DI’s to those of their first primary tumor. Intra-hepatic metastatic tumors exhibited the same DI’s as their primary tumors. Thus, the nuclear DNA ploidy pattern may serve as a stable and valuable marker in predicting the malignant potential and prognosis of HCC.     

Flow cytometric analysis of the nuclear DNA content of hepatocellular carcinoma

The nuclear DNA content of 77 resected specimens from 65 cases of hepatocellular carcinoma (HCC) was measured by means of flow cytometry. The DNA index (DI) was calculated and the correlation between the DNA ploidy pattern and clinicopathological findings was studied. In the cases of HCC with a diameter of less than 5 cm, the 3-year survival rate of the aneuploid cases was 44.5 per cent, which was significantly lower than the 91.4 per cent of the diploid cases (p less than 0.001). Serum AFP levels were over 1000 ng/ml in 46.4 per cent of the aneuploid tumors and 18.5 per cent of the diploid tumors (p less than 0.05). The DI's were investigated in several sites of the same tumor and no difference was seen among the different sites in 16 out of 17 tumors. From 8 recurrent cases out of 12 who underwent a second resection, seven did not show any significant differences in DI from their primary tumor. On the other hand, four cases of second primary tumors showed different DI's to those of their first primary tumor. Intra-hepatic metastatic tumors exhibited the same DI's as their primary tumors. Thus, the nuclear DNA ploidy pattern may serve as a stable and valuable marker in predicting the malignant potential and prognosis of HCC.     

Correlations between nuclear DNA content and nuclear morphometry versus histological grading of prostatic carcinoma

The nuclear area, N/C ratio and anisonucleosis by morphometry and the DNA content by image photo-cytometry of paraffin-embedded tissues of 9 cases of prostatic hypertrophy and 48 cases of carcinoma obtained by open surgery, needle biopsy or by autopsy were correlated with histological grading. In histological grading, in addition to 9 benign hypertrophy cases, 11 were classified as well differentiated adenocarcinoma, 19 as poorly differentiated adenocarcinoma and 1 as small cell carcinoma. All 14 tumors taken from distant metastasis were classified as poorly differentiated adenocarcinoma. Correlation of the data by tumor cell morphometry with those of nuclear image photo-cytometry was carried out on surgical materials alone. In autopsy materials, DNA ploidy patterns were compared between primary lesions and metastases. The DNA histogram patterns of most cases were classified into 4 groups. Hypertrophy was differentiated from carcinoma by the histogram patterns. There were significant correlations between mean DNA value and morphometric factors. One of the 4 histogram patterns had a higher mortality than others. The DNA histograms did not distinguish between the primary and metastatic lesions of the same patients. However, the DNA histograms constructed from metastasis frequently showed a single stem-line of the primary lesion. This study disclosed several correlations between histological grading and morphometrical factors.     

Use and prognostic value of staging mediastinoscopy in non-small-cell lung cancer

One hundred sixty patients had preoperative mediastinoscopy, resection of the primary tumor, and complete mediastinal lymphadenectomy for non-small-cell carcinoma of the lung. Minimum follow-up was 24 months (mean 40 months). Postoperative staging based on histologic examination of the specimen of the lung and mediastinal lymphadenectomy categorized 59 patients in stage I, 28 in stage II, and 73 in stage III (20 T3N0, 12 T3N1, 29 T1 or T2N2, and 12 T3N2). The sensitivity rate of cervical mediastinoscopy for detection of mediastinal node metastasis was 48.7%. False-negative results of mediastinoscopy occurred in 21 of 41 patients with normal mediastinoscopy: unreachable nodes in eight patients, sampling error of reachable nodes in 11 patients, and error on frozen section in two patients. Eleven of 65 patients with clinical stage I disease and normal mediastinum on chest roentgenogram had mediastinal node involvement; only three were detected by mediastinoscopy, which resulted in a low sensitivity rate (27.3%) and a high rate of unnecessary mediastinoscopy (62/65 patients). The sensitivity of mediastinoscopy increased as the amount of disease present, as measured by the clinical stage of disease or positive gallium 67 scan of mediastinum, increased. Eleven of 29 patients with T1 to T2N2 disease discovered at mediastinoscopy had similar survival rates compared with 18 of 29 patients who had a normal mediastinoscopy examination and mediastinal node involvement discovered at thoracotomy.     

Relationship of DNA content to conventional prognostic factors in clinically localised carcinoma of the prostate

One hundred and nine patients treated by total prostatectomy for apparently localised carcinoma were analysed to investigate the prognostic significance of capsular invasion and penetration, seminal vesicle invasion, lymph node metastases, grade as assessed by the Gleason and MD Anderson Hospital (MDAH) systems and DNA content measured by flow cytometry of nuclear material extracted from paraffin embedded tumour. Comparison of DNA content was made with 36 benign prostates. Mean follow-up/survival was 60.7 months, at which time 21 patients had evidence of recurrence or had died. Only 5 patients had local recurrence. Tumour grade, as assessed by both the Gleason Sum Score and the MDAH system, correlated with anatomical extent and was the most important determinant of time to recurrence. Fifty-nine tumours were diploid, 44 tetraploid and 6 aneuploid. One of 36 benign prostates showed aneuploidy. Ploidy did not correlate with the anatomical extent of the tumour or with grade. Tetraploid tumours recurred earlier than diploid tumours. None of 6 aneuploid tumours have recurred, although only 3 have been followed beyond 5 years. Multivariate analysis showed that after accounting for grade, none of the other variables, including ploidy, contributed any additional significant prognostic information. Although the results must be regarded as preliminary, in view of the small number of patients with recurrence, they suggest that DNA content offers limited prognostic information in clinically localised prostate cancer.     

Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no clinical or prognostic significance

The existence of non-small cell lung carcinoma with neuroendocrine differentiation as a distinct entity and its relevance for prognostic and treatment purposes is controversial. This study assesses the frequency and biologic and prognostic significance of neuroendocrine (NE) expression of synaptophysin (SNP), chromogranin (Ch), and neural cell adhesion molecule (N-CAM) using tissue microarray (TMA) and immunohistochemistry. Six hundred nine nonsmall cell lung carcinomas (NSCLCs) were reviewed for subclassification. TMA blocks were made using duplicate 0.6-mm-diameter tissue cores and slides stained with SNP, Ch, and N-CAM. Immunoreactivity was considered if 1% or more of tumor cells were positive. Hematoxylin and eosin-stained sections were subclassified as: 243 adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma, 32 non-small cell carcinoma NOS, and 6 other (carcinosarcoma, giant cell carcinoma). Positivity for either marker was identified in 13.6% of NSCLC (76/558). NSCLC showed reactivity for Ch in 0.4% of cases (2/524), for SNP in 7.5% of cases (39/521) and for N-CAM in 8.6% of cases (44/511), whereas only 0.2% of cases (1/517) showed coexpression of SNP and Ch and none of all 3 markers. The assessment of NE differentiation in NSCLC is unnecessary and expensive and is of no clinical or prognostic significance. SNP or N-CAM stains a small minority of NSCLC, whereas Ch immunoreactivity is less common. Positivity for any 2 NE markers is rare. SNP is more likely to be expressed in adenocarcinoma (P=0.01) and N-CAM in squamous-cell carcinoma (P=0.008). Otherwise there was no correlation between immunoreactivity and tumor morphology. Disease specific and overall survival is not influenced by NE differentiation and therefore non-small cell lung carcinoma with neuroendocrine differentiation should not be a subclass distinct from the other NSCLC.     

Pathologic features of prognostic significance in adrenocortical carcinoma

There are currently no well-established pathologic prognostic factors helpful in distinguishing low versus high grade adrenocortical carcinomas. The effect of 11 pathologic parameters on survival was investigated in 42 cases of adrenocortical carcinoma. Only one variable, mitotic rate, had a strong statistical association with patient outcome. The 21 patients with carcinomas with greater than 20 mitoses per 50 high power fields (hpf) had a median survival of 14 months, whereas the 21 patients with carcinomas with less than or equal to 20 mitoses had a median survival of 58 months (p less than 0.02). The presence of atypical mitoses, capsular invasion, tumor weight greater than 250 g, and size greater than 10 cm each showed a marginal statistical association with poor survival (p less than 0.06), whereas other features assessed, such as nuclear grade, presence of necrosis or of venous or sinusoidal invasion, character of the tumor cell cytoplasm, or architectural pattern, showed no statistical significance in predicting survival. It is proposed that adrenal cortical carcinomas with greater than 20 mitoses be designated high grade, whereas tumors with less than or equal to 20 mitoses be designated low grade.     

The prognostic significance of intranodal isolated tumor cells and micrometastases in patients with non-small cell carcinoma of the lung

OBJECTIVE: To study whether isolated tumor cells and micrometastases, as defined by the current American Joint Committee on Cancer criteria for extrapulmonary neoplasms, have prognostic value for patients with resected non-small cell carcinoma of the lung. METHODS: Intrathoracic lymph nodes (n = 1063) from 60 patients with non-small cell carcinoma of the lung were studied for the presence of metastases with serial histologic sections and keratin immunostains. Metastases were classified as isolated tumor cells, pN1mi, pN1, pN2mi, and pN2. Isolated tumor cells were smaller than 0.2 mm, while pN1mi and pN2mi measured 0.2 mm to 2 mm. Survival analysis was performed, stratifying by nodal status and stage. RESULTS: Isolated tumor cells were detected in 11 lymph nodes from 5 of 33 pN0 patients and in 9 pN1 and pN2 patients. The lymph nodes from 3 patients were reclassified as pN1mi. No pN2mi were detected. A survival model based on a stratification of the cohort into stages I to III was significant (chi-square = 7.426, df = 2, P =.024) but demonstrated considerable overlap between the survival curves of stage I and II patients. A model stratifying isolated tumor cells and pN1mi into stage I disease was significant (chi-square = 7.985, df = 2, P =.018) and showed no overlap between the survival curves of stage I and II patients. There were no significant survival function differences between patients with pN0, isolated tumor cells, and pN1mi. CONCLUSIONS: Patients with non-small cell carcinoma of the lung with isolated tumor cells and pN1mi have similar survivals to those with pN0, consistent with the findings reported for breast cancer patients. Future larger studies of patients with non-small cell carcinoma of the lung are needed to confirm whether current American Joint Committee on Cancer staging criteria should be modified to include the pN1mi category.